Static magnetic field inhibits Epithelial-Mesenchymal Transition (EMT) and metastasis of glioma

Static magnetic field inhibits Epithelial-Mesenchymal Transition (EMT) and metastasis of glioma | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Static magnetic field inhibits Epithelial-Mesenchymal Transition (EMT) and metastasis of glioma Ziyu Sun, Wenxuan Zhao, Xi-feng Fei, Bao He, Lei Shi, Zhen Zhang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5377488/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Apr, 2025 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Gliomas show suboptimal responses to conventional treatments, with tumor cell migration remaining a formidable challenge in glioma therapy. Epithelial-Mesenchymal Transition (EMT) facilitates invasion of glioma cells, and transforming growth factor β1 serves as a potent factor promoting proliferation, migration, and EMT in glioblastoma (GBM). Magnetic fields have been widely applied in the diagnosis and treatment of various diseases, but their effects on the EMT process in glioma cells remain unclear. In this study, we investigated whether a static magnetic field (SMF) could inhibit EMT and metastasis in glioma cells. Conduct functional analysis using U251 and U87 glioma cell lines. The results indicated that cells treated with TGF-β1 increased invasion and migration capabilities, while showing reduced apoptosis. However, when SMFs were combined with TGF-β1 treatment, there was a notable suppression of cell migration and invasion, accompanied by an increase in apoptosis. Additionally, this combination treatment significantly decreased the protein expression of mesenchymal markers N-cadherin and β-catenin, as well as reduced the levels of the recombinant protein MMP-2. Collectively, these findings suggest that SMFs may reduce glioma cell metastasis by inhibiting EMT. Therefore, SMFs could represent a promising therapeutic strategy for diminishing glioma metastasis. Biological sciences/Cancer/Cancer therapy Biological sciences/Cancer/Cns cancer Biological sciences/Cancer/Metastases Biological sciences/Cancer/Tumour biomarkers Glioma magnetic field epithelial-mesenchymal transition TGF-β 1 Figures Figure 1 Figure 2 Figure 3 Introduction The incidence of central nervous system tumors also varies by region. For instance, Europe has the highest incidence rates, with approximately 6.59 per 100,000 population, while in the United States it is around 5.74 per 100,000. In contrast, Asia has the lowest rates, below 3 per 100,000 1 . Gliomas are malignant primary brain tumors believed to originate from neural stem cells or progenitor cells carrying tumor-initiating mutations 2 . They exhibit characteristics of high proliferation, invasion, and poor prognosis, with a median survival period of approximately 14.6 months. The five-year survival rate for glioblastoma (GBM) is 5.1% 3 . The current treatment for glioblastoma is a combination of surgery, radiation therapy, and chemotherapy. However, traditional treatments have proven ineffective in controlling tumor recurrence and metastasis during the therapeutic process. Recent studies suggest that epithelial-mesenchymal transition (EMT) may play a crucial role in tumor invasion and drug resistance. EMT is a reversible process 4 , its characteristics include loss of epithelial cell polarity, reduced cell-cell contact with surrounding cells, decreased intercellular interactions, leading to enhanced cell migration capability. EMT has been proven to play a critical role in embryonic development, but its involvement in tumor metastasis in vivo remains controversial 5 , 6 . For example, during the formation of renal organs, the mesenchyme surrounding the ureteric bud develops into renal epithelium through EMT, which is then followed by the mesenchymal-epithelial transition ( MET) process 7 . Similarly, EMT can facilitate the metastasis of tumor cells. Cancer cells undergo EMT, transitioning from an epithelial to a mesenchymal-like state, acquiring migratory and invasive capabilities to detach from the primary tumor site and migrate to distant locations. Upon reaching a new site, they undergo mesenchymal-epithelial transition (MET) to revert to an epithelial-like state, thereby promoting tumor growth at the metastatic site 8 , 9 . It is believed that cancer cells undergo EMT under the influence of various extracellular signals in the tumor microenvironment 10 . Major pathways involved include TGF-β, Wnt, Notch, and Hedgehog signaling pathways, all of which are associated with the process of EMT. Among these, the TGF-β pathway is likely the main inducer of EMT 11 . In addition, cells exhibiting EMT characteristics typically degrade and invade the basement extracellular matrix by expressing matrix metalloproteinases (MMPs) 12 . The existence of EMT in glioblastoma remains controversial 13 , but the biological process of EMT is significantly associated with the prognosis of glioma patients 14 , indicating a close relationship between EMT progression and poor prognosis in glioblastoma 15 . All organisms are exposed to magnetic fields (MF) daily, which has increased concerns regarding the effects of magnetic fields on human health. Due to the wide spectrum of frequencies, amplitudes, and intensities of magnetic fields, their direct biological targets are not yet fully understood, and their biological effects are diverse 16 . There is evidence that long-term exposure to MF may increase cancer incidence. In 2002, the International Agency for Research on Cancer (IARC) of the World Health Organization (WHO) classified static and extremely low-frequency (ELF) magnetic fields (300 kHz-300 GHz) as possible human carcinogens. However, on the other hand, certain specific intensities of magnetic fields have inhibitory effects on various cancers such as lung cancer 17 and breast cancer 18 . In the case of glioma, cell viability significantly decreases, possibly due to reduced expression of cyclin-dependent kinase 1 protein, rather than apoptosis 19 . In our previous research, it has been confirmed that a static magnetic field of 1000Gs has an inhibitory effect on glioma cells. Importantly, the influence of static magnetic fields on the EMT process in gliomas is largely unknown. This study aims to investigate whether a static magnetic field can inhibit the EMT process in gliomas. Our findings indicate that glioma cells exhibit significant EMT characteristics induced by TGF-β1, and when exposed to a static magnetic field (1000Gs ± 100 Gs), their migration and invasion capabilities markedly diminish. Moreover, there is an increase in apoptotic cell count, along with reduced expression of mesenchymal markers N-cadherin, β-catenin, and recombinant protein MMP-2. These results propose novel therapeutic avenues for glioma treatment. Materials and methods Cell lines and cell culture The human glioblastoma cell lines U87 and U251 were purchased from the Cell Bank of the Chinese Academy of Sciences (Shanghai, China). They were cultured in high-glucose DMEM (Gibco/Biosharp) supplemented with 10% FBS (Gibco) and 1% PS (100 U/ml penicillin and 100 mg/ml streptomycin). GBM cells were maintained at 37°C in a humidified atmosphere containing 5% CO2, with medium changed every 2–3 days. For treatments, cells were supplemented with 10 ng/ml TGF-β1 (PeproTech). Cell cloning and formation experiment U87 (300 cells/well) and U251 (400 cells/well) were seeded into six-well plates. After cell adherence, groups were treated with 10 ng/ml TGF-β1. Cells were allowed to grow for two weeks, fixed with 4% paraformaldehyde (Suzhou Qiangsheng), stained with 2.5% crystal violet solution (Solarbio) for 30 minutes, washed, and then photographed and counted. EdU assay EDU proliferation assay using EdU kit (Beyotime). Cells were seeded in 96-well plates at 3×10^3 cells/well (U87) and 4×10^3 cells/well (U251), and cultured for 72 hours. Overnight, cells were treated with complete medium containing 10 µM EdU labeling reagent. The next day, cells were fixed with 0.5 ml of 4% paraformaldehyde (Suzhou Qiangsheng) for 30 minutes at room temperature, permeabilized with 0.5 ml of permeabilization buffer (Beyotime P0097) for 10–15 minutes at room temperature, and subsequently stained with Apollo staining solution and Hoechst 33342 for 30 minutes each. Images were captured using a fluorescence microscope (Olympus IX73). The proliferation index was calculated as the percentage of EdU-positive cells relative to total cell count. Apoptosis assay Cells were seeded at 3×10^4 cells/well (U87) and 4×10^4 cells/well (U251) in 12-well plates and treated with either a static magnetic field or TGF-β1. After 72 hours, cells were collected and apoptosis was detected using an apoptosis assay kit (KeyGEN BioTECH), followed by flow cytometric analysis (BD FACS-Canto II) according to the manufacturer's instructions. Migration and invasion assays Before the migration assay, cells were starved for 24 hours, then detached with trypsin and resuspended in serum-free medium to a concentration of 4×10^4 cells/ml (U87) and 5×10^4 cells/ml (U251). A total of 200 µl of cell suspension was added to each upper chamber of a 24-well plate, while the lower chamber received 500 µl of complete medium containing 15% FBS with or without 10 ng/ml TGF-β1. For the invasion assay, matrix gel was first coated on the upper chamber, diluted 1:10 in serum-free DMEM, which was pre-cooled at 4°C and kept on ice during the experiment. Sixty microliters of diluted matrix gel was gently added to each insert, ensuring smooth spreading without air bubbles. The plates were incubated in a cell culture incubator for 3 hours at 4°C until the matrix gel solidified completely. Cells were then seeded and incubated under standard conditions for 72 hours. After fixation, cells were stained with crystal violet dye, and the final counting was performed after imaging. Westren blot Cells were lysed using cell lysis buffer (Jiangsu Cowin Biotech) and protein concentrations were determined using a BCA protein assay kit (Jiangsu Cowin Biotech). Equal amounts of protein were separated by SDS-PAGE and transferred onto PVDF membranes, which were then blocked in 10% skim milk prepared in advance and shaken at room temperature for 1 hour. PVDF membranes were then incubated overnight at 4°C with mouse anti-GAPDH (1:2000; ABclonal), N-cadherin (1:5000; Proteintech), β-catenin (1:5000; Proteintech), and rabbit anti-MMP-2 (1:1000; Beyotime).The following day, membranes were shaken at room temperature and washed three times with TBST for ten minutes each. After washing, membranes were incubated at room temperature for 1 hour with corresponding concentrations of goat anti-mouse IgG (Beyotime) and goat anti-rabbit IgG (Beyotime). Subsequently, chemiluminescence and exposure were visualized using an electronic imager (TOUCH IMAGER). Statistical analysis This study employed Photoshop 2020, ImageJ, Flow Jo, and other software for analysis and image processing. All experiments were independently repeated three times. Statistical analyses were performed using GraphPad Prism version 10. P < 0.05 is considered statistically significant. Results TGF-β1 promotes migration and invasion of glioma cells In many cell types, TGF-β1 can inhibit cell proliferation, particularly in epithelial and lymphocytic cells. However, in certain tumor cells, it can paradoxically promote invasion and migration. To investigate the effect of TGF-β1 on glioblastoma cells, U87 and U251 cells were treated with 10 ng/ml of TGF-β1 for 72 hours. As shown in Fig. 1 A, TGF-β1-treated cells underwent morphological changes, adopting a spindle-like morphology resembling mesenchymal cells. In a cloning assay, it was confirmed that TGF-β1 may have a proliferative effect on U87 and U251 cells (Fig. 1 B). To further validate the effect of TGF-β1 treatment on cell proliferation, EdU assay was employed to assess its impact on U87 and U251 cells. As shown in Fig. 1 C, after 72 hours of TGF-β1 intervention, inverted fluorescence microscopy revealed increased proliferation compared to the blank control group, though without statistical significance, indicating that the main effect of TGF - β1 on glioma cells is not on their proliferation ability (U87, P = 0.3824; U251, P = 0.5935). However, apoptosis was significantly reduced in TGF-β1-treated U87 and U251 cells (P < 0.01; P < 0.05; Fig. 1 D).To determine whether TGF-β1's effects are related to migration and invasion, Transwell assays were conducted using U87 and U251 cells treated with TGF-β1 for 72 hours. Compared to the control group, TGF-β1-treated U87 and U251 cells exhibited significantly enhanced migration and invasion abilities (Fig. 1 E). Thus, these data indicate that TGF-β1 can promote migration and invasion capabilities of glioblastoma cells. Magnetic field has an inhibitory effect on glioblastoma cells treated with TGF-β1 To investigate whether a static magnetic field could alter the promoting effect of TGF-β1 on cells, we employed Annexin V/PI dual staining to assess its impact on glioblastoma cell viability. The results showed that the static magnetic field increased the proportion of apoptosis in U87 and U251 cells. After 72 hours of TGF-β1 treatment, apoptosis decreased; however, when TGF-β1 treatment was combined with the static magnetic field, the proportion of apoptotic cells increased again (U87, P < 0.01; U251, P < 0.001; Fig. 2 A). Furthermore, Transwell experiments further confirmed whether the static magnetic field could inhibit the migration and invasion abilities of glioblastoma cells (Fig. 2 B). Compared to the control group, the magnetic field could suppress the migration and invasion capabilities of both U87 and U251 cells, and could reverse the promoting effect of TGF-β1. The static magnetic field can regulate the expression of EMT-related genes in glioblastoma cells To confirm whether the static magnetic field regulates the expression of EMT-related genes, we conducted Western Blot analysis. We assessed the protein expression of EMT markers using Western Blot analysis, which revealed that compared to the control group, U87 and U251 cells exposed solely to the static magnetic field showed decreased protein levels of mesenchymal markers N-cadherin and β-catenin, as well as reduced expression of the recombinant protein MMP-2. After 72 hours of treatment with TGF-β1 (10 ng/ml), U87 and U251 cells exhibited significantly increased protein expression of N-cadherin, β-catenin, and MMP-2. However, When a static magnetic field is combined with TGF-β1, the co-expression of N-cadherin, β-catenin, and MMP-2 was relatively reduced compared to TGF-β1 treatment alone (Fig. 3 ). In summary, these results indicate that the static magnetic field can inhibit TGF-β 1-induced EMT. Discussion This study investigates the inhibitory effects of a static magnetic field (SMF, 1000 ± 100 Gs) on the epithelial-mesenchymal transition (EMT) in glioma cells. Our findings demonstrate that SMF exerts a significant suppressive effect on EMT induced by TGF-β1 in glioma cells, reducing migration and invasion capabilities while notably increasing apoptosis. Through Western Blot analysis, we observed that SMF treatment decreased the expression of key EMT markers, including N-cadherin, β-catenin, and MMP-2. These results highlight the potential of SMF as an adjuvant in glioma therapy, offering a novel approach to counteract tumor metastasis. First, our findings align with previous research showing that TGF-β1, as a primary inducer of EMT, enhances glioma cell migration and invasion 20 , 21 . TGF-β1 induces morphological changes in cells, promoting a mesenchymal phenotype and increasing cell invasiveness. This is consistent with earlier studies that underscore the pivotal role of TGF-β signaling in advancing malignancy in glioma cells 22 . Although the mechanisms underlying TGF-β-induced EMT have been extensively studied, the process remains complex and varied depending on the microenvironment 23 , 24 . As a result, inhibiting TGF-β1-induced EMT is a critical challenge in glioma treatment. The application of SMF in glioma treatment remains in an exploratory phase. Previous studies have shown that SMF can inhibit cell proliferation and promote apoptosis in certain tumor types 25 , 26 . Our findings reveal that SMF markedly suppresses TGF-β1-induced EMT, significantly reducing migration and invasion capabilities in glioma cells. Specifically, SMF treatment downregulated N-cadherin and β-catenin expression, markers commonly associated with decreased cell-cell adhesion and increased motility 27 . Additionally, the downregulation of MMP-2 likely plays a role in reducing basement membrane and extracellular matrix degradation 28 , thus restricting the invasive behavior of glioma cells. The impact of SMF on apoptosis is another significant finding of this study. While apoptosis decreased significantly in TGF-β1-treated glioma cells, the combination of TGF-β1 and SMF notably increased apoptotic rates, suggesting a distinct mechanism by which SMF enhances cell apoptosis. Previous studies suggest that SMF may inhibit glioma cell proliferation by affecting the expression of cell cycle-related proteins 19 . However, our results indicate that SMF's mechanism of action in promoting apoptosis and suppressing EMT might operate independently of its effects on cell proliferation. Future studies should explore the specific regulatory effects of SMF on apoptotic signaling pathways in glioma cells to elucidate its therapeutic mechanism. Furthermore, this study proposes a potential therapeutic strategy utilizing SMF as an inhibitor of TGF-β1-induced EMT. Due to the complexity of the TGF-β signaling pathway 29 , direct inhibition presents certain challenges and potential side effects 30 . SMF, as a non-invasive physical intervention, may effectively reduce glioma cell migration and invasion by downregulating EMT-related markers and promoting apoptosis. However, given that the biological effects of SMF vary depending on experimental conditions such as field strength, exposure duration, and cell type 31 , additional in vivo experiments are essential to validate SMF's therapeutic efficacy and safety. In conclusion, this study provides novel insights into the inhibitory role of static magnetic fields in TGF-β1-induced EMT, significantly reducing glioma cell migration and invasiveness. SMF may serve as a unique physical intervention by downregulating EMT-related markers and promoting apoptosis, offering a promising adjunct to glioma treatment. Given the variability in SMF effects across cell types and in vivo conditions, future research should further investigate SMF's mechanisms in glioma treatment to optimize clinical applications. Declarations Acknowledgements This work was supported by the National Natural Science Foundation of China (82273472), Suzhou Key Laboratory of Neuro-Oncology and Nano-Bionics, Suzhou Medical and Health Innovation Project (SKYD2022002) and Suzhou Health Key Medical Talent Training Project (GSWS2020112). The funders had no role in the study design, data collection and analysis, decision to publish, or in the preparation of the manuscript. Author contributions ZS and WZ performed most of the experiments, treated data, and wrote the manuscript. ZS performed mouse treatment experiments. LS, ZZ and SC participated in research conception and design, and revised the manuscript. XF and BH supervised experiments and contributed to analytic tools. All authors read and approve the final version of the manuscript. Data availability The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. Ethics approval and consent to participate The studies involving human participants were reviewed and approved by the Ethics Committee of The First people’s Hospital of Kunshan. The participants provided their written informed consent to participate in this study. All animal studies obtained the approval of the Institutional Animal Care and Use Committee of The First people’s Hospital of Kunshan and implemented in line with institutional and national guidelines (No. 2021-06-004-H01). Declaration of Generative AI and AI-assisted technologies in the writing process During the preparation of this work the authors used Chatgpt in order to proceed language modification. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication. References Leece, R. et al. Global incidence of malignant brain and other central nervous system tumors by histology, 2003–2007. Neuro-Oncol 19 , 1553–1564 (2017). Weller, M. et al. Glioma. Nat. Rev. Dis. Primer 10 , 33 (2024). Ostrom, Q. T. et al. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2008–2012. Neuro-Oncol 17 , iv1–iv62 (2015). Nieto, M. A. Epithelial-Mesenchymal Transitions in development and disease: old views and new perspectives. Int. J. Dev. Biol. 53 , 1541–1547 (2009). Ledford, H. Cancer theory faces doubts. Nature 472 , 273–273 (2011). Thompson, E. W. & Newgreen, D. F. Carcinoma Invasion and Metastasis: A Role for Epithelial-Mesenchymal Transition? Cancer Res. 65 , 5991–5995 (2005). Hay, E. D. & Zuk, A. Transformations between epithelium and mesenchyme: Normal, pathological, and experimentally induced. Am. J. Kidney Dis. 26 , 678–690 (1995). Tsai, J. H., Donaher, J. L., Murphy, D. A., Chau, S. & Yang, J. Spatiotemporal Regulation of Epithelial-Mesenchymal Transition is Essential for Squamous Cell Carcinoma Metastasis. (2013). Ocaña, O. H. et al. Metastatic Colonization Requires the Repression of the Epithelial-Mesenchymal Transition Inducer Prrx1. Cancer Cell. 22 , 709–724 (2012). Tsai, J. H. & Yang J. Epithelial–mesenchymal plasticity in carcinoma metastasis. Katsuno, Y., Lamouille, S. & Derynck, R. TGF-b signaling and epithelial–mesenchymal transition in cancer progression. 25 , (2013). Lu, W. & Kang, Y. Epithelial-Mesenchymal Plasticity in Cancer Progression and Metastasis. Dev. Cell. 49 , 361–374 (2019). Iser, I. C., Pereira, M. B., Lenz, G. & Wink, M. R. The Epithelial-to‐Mesenchymal Transition‐Like Process in Glioblastoma: An Updated Systematic Review and In Silico Investigation. Med. Res. Rev. 37 , 271–313 (2017). Ning, W. et al. The Prognostic Value of EMT in Glioma and its Role in the Glioma Immune Microenvironment. J. Mol. Neurosci. 70 , 1501–1511 (2020). Yang, Y. et al. BDKRB2 is a novel EMT-related biomarker and predicts poor survival in glioma. Aging 13 , 7499–7516 (2021). Kimsa-Dudek, M., Krawczyk, A., Synowiec‐Wojtarowicz, A., Dudek, S. & Pawłowska‐Góral, K. The impact of the co‐exposure of melanoma cells to chlorogenic acid and a moderate‐strength static magnetic field. J. Food Biochem. 44 , (2020). Yang, X. et al. An upward 9.4 T static magnetic field inhibits DNA synthesis and increases ROS-P53 to suppress lung cancer growth. Transl Oncol. 14 , 101103 (2021). Fan, Z. et al. A Static Magnetic Field Inhibits the Migration and Telomerase Function of Mouse Breast Cancer Cells. BioMed Res. Int. 1–9 (2020). (2020). Kim, S. C., Im, W., Shim, J. Y., Kim, S. K. & Kim, B. J. Static magnetic field controls cell cycle in cultured human glioblastoma cells. Cytotechnology 68 , 2745–2751 (2016). Lee, S. H. et al. The Effects of Retinoic Acid and MAPK Inhibitors on Phosphorylation of Smad2/3 Induced by Transforming Growth Factor β1. Tuberc Respir Dis. 82 , 42 (2019). Kim, B. N. et al. TGF-β induced EMT and stemness characteristics are associated with epigenetic regulation in lung cancer. Sci. Rep. 10 , 10597 (2020). Kaminska, B. & Cyranowski, S. Recent Advances in Understanding Mechanisms of TGF Beta Signaling and Its Role in Glioma Pathogenesis. in Glioma Signaling (ed Barańska, J.) vol 1202 179–201 (Springer International Publishing, Cham, (2020). Miyazono, K., Ehata, S. & Koinuma, D. Tumor-promoting functions of transforming growth factor-β in progression of cancer. Ups J. Med. Sci. 117 , 143–152 (2012). Birch, J. L. et al. Multifaceted transforming growth factor-beta (TGFβ) signalling in glioblastoma. Cell. Signal. 72 , 109638 (2020). Aiello, N. M. & Kang, Y. Context-dependent EMT programs in cancer metastasis. Chaffer, C. L. EMT, cell plasticity and metastasis. Cancer Metastasis Rev. (2016). Loh, C. Y. et al. The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges. Cells 8 , 1118 (2019). Roomi, M. W., Kalinovsky, T., Rath, M. & Niedzwiecki, A. Modulation of MMP-2 and MMP-9 secretion by cytokines, inducers and inhibitors in human glioblastoma T-98G cells. Oncol. Rep. 37 , 1907–1913 (2017). Peng, D. Targeting TGF-β signal transduction for fibrosis and cancer therapy. (2022). Derynck, R., Turley, S. J. & Akhurst, R. J. TGFβ biology in cancer progression and immunotherapy. Nat. Rev. Clin. Oncol. 18 , 9–34 (2021). Robison, J. G., Pendleton, A. R., Monson, K. O., Murray, B. K. & O’Neill, K. L. Decreased DNA repair rates and protection from heat induced apoptosis mediated by electromagnetic field exposure. Bioelectromagnetics 23 , 106–112 (2002). Additional Declarations No competing interests reported. Supplementary Files SupplementaryFile.zip WesternBlotStripDescription.docx Cite Share Download PDF Status: Published Journal Publication published 11 Apr, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 18 Dec, 2024 Reviews received at journal 16 Dec, 2024 Reviewers agreed at journal 11 Dec, 2024 Reviews received at journal 02 Dec, 2024 Reviewers agreed at journal 01 Dec, 2024 Reviewers invited by journal 30 Nov, 2024 Editor assigned by journal 30 Nov, 2024 Editor invited by journal 18 Nov, 2024 Submission checks completed at journal 16 Nov, 2024 First submitted to journal 02 Nov, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5377488","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":389172852,"identity":"cac70028-e37b-4aa5-86e5-1f378dfd4bd6","order_by":0,"name":"Ziyu Sun","email":"","orcid":"","institution":"Gusu School, Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ziyu","middleName":"","lastName":"Sun","suffix":""},{"id":389172853,"identity":"fa80ba59-0c61-4a6c-9a74-eeb7845ea1c8","order_by":1,"name":"Wenxuan Zhao","email":"","orcid":"","institution":"Gusu School, Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wenxuan","middleName":"","lastName":"Zhao","suffix":""},{"id":389172854,"identity":"1f70a82e-314f-492b-b7a2-036b12d9a1e3","order_by":2,"name":"Xi-feng Fei","email":"","orcid":"","institution":"Shanghai Jiao Tong University","correspondingAuthor":false,"prefix":"","firstName":"Xi-feng","middleName":"","lastName":"Fei","suffix":""},{"id":389172855,"identity":"55e86e15-5ab0-4c98-8b75-7db37b8d44f1","order_by":3,"name":"Bao He","email":"","orcid":"","institution":"First People's Hospital of Kunshan","correspondingAuthor":false,"prefix":"","firstName":"Bao","middleName":"","lastName":"He","suffix":""},{"id":389172856,"identity":"2265abf2-8b41-4eab-b242-2fc674efebce","order_by":4,"name":"Lei Shi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzklEQVRIie3RMQrCMBSA4RcEp0rXTHqF56x4FkuhXUQKQucUwamzFHqK3iAhq9S10A71Bh07VDC1utq4CebfXshHHgTAZPrFKIk44BoI66epHmGKeF8RAA4gX5MOWaRHxpvgup+cLwhNKMFO2WeClWAiwfJA0h2SJJdAKz5CqMOkhaUTKTKZnaQ62Y4slijSYT6Quw6BQhFAPhCiQ1AREaOriBeIOPctWowu5t/qtts4WepmdRuu5nYytti7JXt+EFia9/vn9K+aTCbTv/UARLBJrbafAP0AAAAASUVORK5CYII=","orcid":"","institution":"Gusu School, Nanjing Medical University","correspondingAuthor":true,"prefix":"","firstName":"Lei","middleName":"","lastName":"Shi","suffix":""},{"id":389172857,"identity":"74f0a0ff-0a1a-4934-bbbe-d209ef43b932","order_by":5,"name":"Zhen Zhang","email":"","orcid":"","institution":"China Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhen","middleName":"","lastName":"Zhang","suffix":""},{"id":389172858,"identity":"d6cfa6ed-bbed-471e-94d3-c3a1572144f2","order_by":6,"name":"Shi-zhong Cai","email":"","orcid":"","institution":"Children's Hospital of Suzhou University","correspondingAuthor":false,"prefix":"","firstName":"Shi-zhong","middleName":"","lastName":"Cai","suffix":""}],"badges":[],"createdAt":"2024-11-02 09:38:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5377488/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5377488/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-96047-x","type":"published","date":"2025-04-11T16:05:06+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":71500019,"identity":"139c0daa-80c9-435c-8d08-9965ca5f708a","added_by":"auto","created_at":"2024-12-16 08:57:01","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":899200,"visible":true,"origin":"","legend":"\u003cp\u003eTGF-β promotes the proliferation, migration, and invasion of glioma cells. (A) Changes in the state of U87 and U251 cells after TGF-β1 treatment observed under an inverted (fluorescence) microscope at 10× magnification; (B and C) The effect of TGF-β1 on the proliferation ability of U87 and U251 cells; (D) A significant reduction in the number of apoptotic cells under TGF-β1 intervention compared to the control group; (E) Changes in the migration and invasion abilities of U87 and U251 cells under TGF-β1 treatment. ns: p\u0026gt;0.05; *: p\u0026lt;0.05; **: p\u0026lt;0.01; ***: p\u0026lt;0.001; ****: p\u0026lt;0.0001.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5377488/v1/c4140933695a062dd70df568.jpeg"},{"id":71500023,"identity":"a7438ba6-ca46-4797-b343-6fe7f09976ab","added_by":"auto","created_at":"2024-12-16 08:57:01","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1242768,"visible":true,"origin":"","legend":"\u003cp\u003eStatic magnetic field inhibits TGF-β1-treated glioma cells. (A) The static magnetic field increases cell apoptosis; after 72 hours of TGF-β1 treatment, apoptosis decreases, but it increases with combined treatment. (B) The static magnetic field inhibits cell migration and invasion, whereas TGF-β1 enhances cell proliferation and invasion; combined treatment reduces cell migration and invasion. ns: p\u0026gt;0.05; *: p\u0026lt;0.05; **: p\u0026lt;0.01; ***: p\u0026lt;0.001; ****: p\u0026lt;0.0001.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5377488/v1/8eb013faad5c01af9cde49a6.jpeg"},{"id":71500021,"identity":"0d0d099a-7ab8-4cd8-8cc1-7095840e3b5b","added_by":"auto","created_at":"2024-12-16 08:57:01","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":632829,"visible":true,"origin":"","legend":"\u003cp\u003eStatic magnetic field regulates the expression of EMT-related genes in glioma cells. Expression of EMT-related proteins in U87 and U251 cells under TGF-β1 and static magnetic field intervention. ns: p\u0026gt;0.05; *: p\u0026lt;0.05; **: p\u0026lt;0.01; ***: p\u0026lt;0.001; ****: p\u0026lt;0.0001.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5377488/v1/4181a3f0ba30b91d56a02863.jpeg"},{"id":80558443,"identity":"8ada8e57-6530-4e60-884e-571abba82299","added_by":"auto","created_at":"2025-04-14 16:14:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3417428,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5377488/v1/a6d1b362-fa23-4919-8422-81678874e9fb.pdf"},{"id":71500024,"identity":"90f37f67-1f88-489c-83b5-57b709dea7a2","added_by":"auto","created_at":"2024-12-16 08:57:02","extension":"zip","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":34331830,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFile.zip","url":"https://assets-eu.researchsquare.com/files/rs-5377488/v1/d341c2a9e92aecedf693fd0a.zip"},{"id":71500022,"identity":"e6a445d8-b4dd-4f06-b07e-d3d112b92583","added_by":"auto","created_at":"2024-12-16 08:57:01","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":10338,"visible":true,"origin":"","legend":"","description":"","filename":"WesternBlotStripDescription.docx","url":"https://assets-eu.researchsquare.com/files/rs-5377488/v1/d23a011437bb30fdb1ccb61d.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Static magnetic field inhibits Epithelial-Mesenchymal Transition (EMT) and metastasis of glioma","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe incidence of central nervous system tumors also varies by region. For instance, Europe has the highest incidence rates, with approximately 6.59 per 100,000 population, while in the United States it is around 5.74 per 100,000. In contrast, Asia has the lowest rates, below 3 per 100,000\u003csup\u003e1\u003c/sup\u003e. Gliomas are malignant primary brain tumors believed to originate from neural stem cells or progenitor cells carrying tumor-initiating mutations\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. They exhibit characteristics of high proliferation, invasion, and poor prognosis, with a median survival period of approximately 14.6 months. The five-year survival rate for glioblastoma (GBM) is 5.1%\u003csup\u003e3\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe current treatment for glioblastoma is a combination of surgery, radiation therapy, and chemotherapy. However, traditional treatments have proven ineffective in controlling tumor recurrence and metastasis during the therapeutic process. Recent studies suggest that epithelial-mesenchymal transition (EMT) may play a crucial role in tumor invasion and drug resistance. EMT is a reversible process\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e, its characteristics include loss of epithelial cell polarity, reduced cell-cell contact with surrounding cells, decreased intercellular interactions, leading to enhanced cell migration capability. EMT has been proven to play a critical role in embryonic development, but its involvement in tumor metastasis in vivo remains controversial\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. For example, during the formation of renal organs, the mesenchyme surrounding the ureteric bud develops into renal epithelium through EMT, which is then followed by the mesenchymal-epithelial transition \u003cb\u003e(\u003c/b\u003eMET) process\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Similarly, EMT can facilitate the metastasis of tumor cells. Cancer cells undergo EMT, transitioning from an epithelial to a mesenchymal-like state, acquiring migratory and invasive capabilities to detach from the primary tumor site and migrate to distant locations. Upon reaching a new site, they undergo mesenchymal-epithelial transition (MET) to revert to an epithelial-like state, thereby promoting tumor growth at the metastatic site\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. It is believed that cancer cells undergo EMT under the influence of various extracellular signals in the tumor microenvironment\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Major pathways involved include TGF-β, Wnt, Notch, and Hedgehog signaling pathways, all of which are associated with the process of EMT. Among these, the TGF-β pathway is likely the main inducer of EMT\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. In addition, cells exhibiting EMT characteristics typically degrade and invade the basement extracellular matrix by expressing matrix metalloproteinases (MMPs)\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. The existence of EMT in glioblastoma remains controversial\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e, but the biological process of EMT is significantly associated with the prognosis of glioma patients\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e, indicating a close relationship between EMT progression and poor prognosis in glioblastoma\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAll organisms are exposed to magnetic fields (MF) daily, which has increased concerns regarding the effects of magnetic fields on human health. Due to the wide spectrum of frequencies, amplitudes, and intensities of magnetic fields, their direct biological targets are not yet fully understood, and their biological effects are diverse\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. There is evidence that long-term exposure to MF may increase cancer incidence. In 2002, the International Agency for Research on Cancer (IARC) of the World Health Organization (WHO) classified static and extremely low-frequency (ELF) magnetic fields (300 kHz-300 GHz) as possible human carcinogens. However, on the other hand, certain specific intensities of magnetic fields have inhibitory effects on various cancers such as lung cancer\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e and breast cancer\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. In the case of glioma, cell viability significantly decreases, possibly due to reduced expression of cyclin-dependent kinase 1 protein, rather than apoptosis\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. In our previous research, it has been confirmed that a static magnetic field of 1000Gs has an inhibitory effect on glioma cells. Importantly, the influence of static magnetic fields on the EMT process in gliomas is largely unknown.\u003c/p\u003e \u003cp\u003eThis study aims to investigate whether a static magnetic field can inhibit the EMT process in gliomas. Our findings indicate that glioma cells exhibit significant EMT characteristics induced by TGF-β1, and when exposed to a static magnetic field (1000Gs\u0026thinsp;\u0026plusmn;\u0026thinsp;100 Gs), their migration and invasion capabilities markedly diminish. Moreover, there is an increase in apoptotic cell count, along with reduced expression of mesenchymal markers N-cadherin, β-catenin, and recombinant protein MMP-2. These results propose novel therapeutic avenues for glioma treatment.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eCell lines and cell culture\u003c/h2\u003e \u003cp\u003eThe human glioblastoma cell lines U87 and U251 were purchased from the Cell Bank of the Chinese Academy of Sciences (Shanghai, China). They were cultured in high-glucose DMEM (Gibco/Biosharp) supplemented with 10% FBS (Gibco) and 1% PS (100 U/ml penicillin and 100 mg/ml streptomycin). GBM cells were maintained at 37\u0026deg;C in a humidified atmosphere containing 5% CO2, with medium changed every 2\u0026ndash;3 days. For treatments, cells were supplemented with 10 ng/ml TGF-β1 (PeproTech).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCell cloning and formation experiment\u003c/h3\u003e\n\u003cp\u003eU87 (300 cells/well) and U251 (400 cells/well) were seeded into six-well plates. After cell adherence, groups were treated with 10 ng/ml TGF-β1. Cells were allowed to grow for two weeks, fixed with 4% paraformaldehyde (Suzhou Qiangsheng), stained with 2.5% crystal violet solution (Solarbio) for 30 minutes, washed, and then photographed and counted.\u003c/p\u003e\n\u003ch3\u003eEdU assay\u003c/h3\u003e\n\u003cp\u003eEDU proliferation assay using EdU kit (Beyotime). Cells were seeded in 96-well plates at 3\u0026times;10^3 cells/well (U87) and 4\u0026times;10^3 cells/well (U251), and cultured for 72 hours. Overnight, cells were treated with complete medium containing 10 \u0026micro;M EdU labeling reagent. The next day, cells were fixed with 0.5 ml of 4% paraformaldehyde (Suzhou Qiangsheng) for 30 minutes at room temperature, permeabilized with 0.5 ml of permeabilization buffer (Beyotime P0097) for 10\u0026ndash;15 minutes at room temperature, and subsequently stained with Apollo staining solution and Hoechst 33342 for 30 minutes each. Images were captured using a fluorescence microscope (Olympus IX73). The proliferation index was calculated as the percentage of EdU-positive cells relative to total cell count.\u003c/p\u003e\n\u003ch3\u003eApoptosis assay\u003c/h3\u003e\n\u003cp\u003eCells were seeded at 3\u0026times;10^4 cells/well (U87) and 4\u0026times;10^4 cells/well (U251) in 12-well plates and treated with either a static magnetic field or TGF-β1. After 72 hours, cells were collected and apoptosis was detected using an apoptosis assay kit (KeyGEN BioTECH), followed by flow cytometric analysis (BD FACS-Canto II) according to the manufacturer's instructions.\u003c/p\u003e\n\u003ch3\u003eMigration and invasion assays\u003c/h3\u003e\n\u003cp\u003eBefore the migration assay, cells were starved for 24 hours, then detached with trypsin and resuspended in serum-free medium to a concentration of 4\u0026times;10^4 cells/ml (U87) and 5\u0026times;10^4 cells/ml (U251). A total of 200 \u0026micro;l of cell suspension was added to each upper chamber of a 24-well plate, while the lower chamber received 500 \u0026micro;l of complete medium containing 15% FBS with or without 10 ng/ml TGF-β1. For the invasion assay, matrix gel was first coated on the upper chamber, diluted 1:10 in serum-free DMEM, which was pre-cooled at 4\u0026deg;C and kept on ice during the experiment. Sixty microliters of diluted matrix gel was gently added to each insert, ensuring smooth spreading without air bubbles. The plates were incubated in a cell culture incubator for 3 hours at 4\u0026deg;C until the matrix gel solidified completely. Cells were then seeded and incubated under standard conditions for 72 hours. After fixation, cells were stained with crystal violet dye, and the final counting was performed after imaging.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eWestren blot\u003c/h2\u003e \u003cp\u003eCells were lysed using cell lysis buffer (Jiangsu Cowin Biotech) and protein concentrations were determined using a BCA protein assay kit (Jiangsu Cowin Biotech). Equal amounts of protein were separated by SDS-PAGE and transferred onto PVDF membranes, which were then blocked in 10% skim milk prepared in advance and shaken at room temperature for 1 hour. PVDF membranes were then incubated overnight at 4\u0026deg;C with mouse anti-GAPDH (1:2000; ABclonal), N-cadherin (1:5000; Proteintech), β-catenin (1:5000; Proteintech), and rabbit anti-MMP-2 (1:1000; Beyotime).The following day, membranes were shaken at room temperature and washed three times with TBST for ten minutes each. After washing, membranes were incubated at room temperature for 1 hour with corresponding concentrations of goat anti-mouse IgG (Beyotime) and goat anti-rabbit IgG (Beyotime). Subsequently, chemiluminescence and exposure were visualized using an electronic imager (TOUCH IMAGER).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThis study employed Photoshop 2020, ImageJ, Flow Jo, and other software for analysis and image processing. All experiments were independently repeated three times. Statistical analyses were performed using GraphPad Prism version 10. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 is considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eTGF-β1 promotes migration and invasion of glioma cells\u003c/h2\u003e \u003cp\u003eIn many cell types, TGF-β1 can inhibit cell proliferation, particularly in epithelial and lymphocytic cells. However, in certain tumor cells, it can paradoxically promote invasion and migration. To investigate the effect of TGF-β1 on glioblastoma cells, U87 and U251 cells were treated with 10 ng/ml of TGF-β1 for 72 hours. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA, TGF-β1-treated cells underwent morphological changes, adopting a spindle-like morphology resembling mesenchymal cells. In a cloning assay, it was confirmed that TGF-β1 may have a proliferative effect on U87 and U251 cells (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). To further validate the effect of TGF-β1 treatment on cell proliferation, EdU assay was employed to assess its impact on U87 and U251 cells. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC, after 72 hours of TGF-β1 intervention, inverted fluorescence microscopy revealed increased proliferation compared to the blank control group, though without statistical significance, indicating that the main effect of TGF - β1 on glioma cells is not on their proliferation ability (U87, P\u0026thinsp;=\u0026thinsp;0.3824; U251, P\u0026thinsp;=\u0026thinsp;0.5935).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eHowever, apoptosis was significantly reduced in TGF-β1-treated U87 and U251 cells (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01; P\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD).To determine whether TGF-β1's effects are related to migration and invasion, Transwell assays were conducted using U87 and U251 cells treated with TGF-β1 for 72 hours. Compared to the control group, TGF-β1-treated U87 and U251 cells exhibited significantly enhanced migration and invasion abilities (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eE). Thus, these data indicate that TGF-β1 can promote migration and invasion capabilities of glioblastoma cells.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eMagnetic field has an inhibitory effect on glioblastoma cells treated with TGF-β1\u003c/h2\u003e \u003cp\u003eTo investigate whether a static magnetic field could alter the promoting effect of TGF-β1 on cells, we employed Annexin V/PI dual staining to assess its impact on glioblastoma cell viability. The results showed that the static magnetic field increased the proportion of apoptosis in U87 and U251 cells. After 72 hours of TGF-β1 treatment, apoptosis decreased; however, when TGF-β1 treatment was combined with the static magnetic field, the proportion of apoptotic cells increased again (U87, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01; U251, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). Furthermore, Transwell experiments further confirmed whether the static magnetic field could inhibit the migration and invasion abilities of glioblastoma cells (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). Compared to the control group, the magnetic field could suppress the migration and invasion capabilities of both U87 and U251 cells, and could reverse the promoting effect of TGF-β1.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eThe static magnetic field can regulate the expression of EMT-related genes in glioblastoma cells\u003c/h2\u003e \u003cp\u003eTo confirm whether the static magnetic field regulates the expression of EMT-related genes, we conducted Western Blot analysis. We assessed the protein expression of EMT markers using Western Blot analysis, which revealed that compared to the control group, U87 and U251 cells exposed solely to the static magnetic field showed decreased protein levels of mesenchymal markers N-cadherin and β-catenin, as well as reduced expression of the recombinant protein MMP-2. After 72 hours of treatment with TGF-β1 (10 ng/ml), U87 and U251 cells exhibited significantly increased protein expression of N-cadherin, β-catenin, and MMP-2. However, When a static magnetic field is combined with TGF-β1, the co-expression of N-cadherin, β-catenin, and MMP-2 was relatively reduced compared to TGF-β1 treatment alone (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In summary, these results indicate that the static magnetic field can inhibit TGF-β 1-induced EMT.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study investigates the inhibitory effects of a static magnetic field (SMF, 1000\u0026thinsp;\u0026plusmn;\u0026thinsp;100 Gs) on the epithelial-mesenchymal transition (EMT) in glioma cells. Our findings demonstrate that SMF exerts a significant suppressive effect on EMT induced by TGF-β1 in glioma cells, reducing migration and invasion capabilities while notably increasing apoptosis. Through Western Blot analysis, we observed that SMF treatment decreased the expression of key EMT markers, including N-cadherin, β-catenin, and MMP-2. These results highlight the potential of SMF as an adjuvant in glioma therapy, offering a novel approach to counteract tumor metastasis.\u003c/p\u003e \u003cp\u003eFirst, our findings align with previous research showing that TGF-β1, as a primary inducer of EMT, enhances glioma cell migration and invasion\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. TGF-β1 induces morphological changes in cells, promoting a mesenchymal phenotype and increasing cell invasiveness. This is consistent with earlier studies that underscore the pivotal role of TGF-β signaling in advancing malignancy in glioma cells\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Although the mechanisms underlying TGF-β-induced EMT have been extensively studied, the process remains complex and varied depending on the microenvironment\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. As a result, inhibiting TGF-β1-induced EMT is a critical challenge in glioma treatment.\u003c/p\u003e \u003cp\u003eThe application of SMF in glioma treatment remains in an exploratory phase. Previous studies have shown that SMF can inhibit cell proliferation and promote apoptosis in certain tumor types\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. Our findings reveal that SMF markedly suppresses TGF-β1-induced EMT, significantly reducing migration and invasion capabilities in glioma cells. Specifically, SMF treatment downregulated N-cadherin and β-catenin expression, markers commonly associated with decreased cell-cell adhesion and increased motility\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. Additionally, the downregulation of MMP-2 likely plays a role in reducing basement membrane and extracellular matrix degradation\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e, thus restricting the invasive behavior of glioma cells.\u003c/p\u003e \u003cp\u003eThe impact of SMF on apoptosis is another significant finding of this study. While apoptosis decreased significantly in TGF-β1-treated glioma cells, the combination of TGF-β1 and SMF notably increased apoptotic rates, suggesting a distinct mechanism by which SMF enhances cell apoptosis. Previous studies suggest that SMF may inhibit glioma cell proliferation by affecting the expression of cell cycle-related proteins\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. However, our results indicate that SMF's mechanism of action in promoting apoptosis and suppressing EMT might operate independently of its effects on cell proliferation. Future studies should explore the specific regulatory effects of SMF on apoptotic signaling pathways in glioma cells to elucidate its therapeutic mechanism.\u003c/p\u003e \u003cp\u003eFurthermore, this study proposes a potential therapeutic strategy utilizing SMF as an inhibitor of TGF-β1-induced EMT. Due to the complexity of the TGF-β signaling pathway\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e, direct inhibition presents certain challenges and potential side effects\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. SMF, as a non-invasive physical intervention, may effectively reduce glioma cell migration and invasion by downregulating EMT-related markers and promoting apoptosis. However, given that the biological effects of SMF vary depending on experimental conditions such as field strength, exposure duration, and cell type\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e, additional in vivo experiments are essential to validate SMF's therapeutic efficacy and safety.\u003c/p\u003e \u003cp\u003eIn conclusion, this study provides novel insights into the inhibitory role of static magnetic fields in TGF-β1-induced EMT, significantly reducing glioma cell migration and invasiveness. SMF may serve as a unique physical intervention by downregulating EMT-related markers and promoting apoptosis, offering a promising adjunct to glioma treatment. Given the variability in SMF effects across cell types and in vivo conditions, future research should further investigate SMF's mechanisms in glioma treatment to optimize clinical applications.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Natural Science Foundation of China (82273472), Suzhou Key Laboratory of Neuro-Oncology and Nano-Bionics, Suzhou Medical and Health Innovation Project (SKYD2022002) and Suzhou Health Key Medical Talent Training Project (GSWS2020112). The funders had no role in the study design, data collection and analysis, decision to publish, or in the preparation of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZS and WZ performed most of the experiments, treated data, and wrote the manuscript. ZS performed mouse treatment experiments. LS, ZZ and SC participated in research conception and design, and revised the manuscript. XF and BH supervised experiments and contributed to analytic tools. All authors read and approve the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe studies involving human participants were reviewed and approved by the Ethics\u003c/p\u003e\n\u003cp\u003eCommittee of The First people\u0026rsquo;s Hospital of Kunshan. The participants provided\u003c/p\u003e\n\u003cp\u003etheir written informed consent to participate in this study. All animal studies obtained the approval of the Institutional Animal Care and Use Committee of The First people\u0026rsquo;s Hospital of Kunshan and implemented in line with institutional and national guidelines (No. 2021-06-004-H01).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of Generative AI and AI-assisted technologies in the\u003c/strong\u003e\u003cstrong\u003ewriting process\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring the preparation of this work the authors used Chatgpt in order to proceed language modification. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLeece, R. et al. Global incidence of malignant brain and other central nervous system tumors by histology, 2003\u0026ndash;2007. \u003cem\u003eNeuro-Oncol\u003c/em\u003e \u003cb\u003e19\u003c/b\u003e, 1553\u0026ndash;1564 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWeller, M. et al. Glioma. \u003cem\u003eNat. Rev. Dis. Primer\u003c/em\u003e \u003cb\u003e10\u003c/b\u003e, 33 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOstrom, Q. T. et al. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2008\u0026ndash;2012. \u003cem\u003eNeuro-Oncol\u003c/em\u003e \u003cb\u003e17\u003c/b\u003e, iv1\u0026ndash;iv62 (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNieto, M. A. Epithelial-Mesenchymal Transitions in development and disease: old views and new perspectives. \u003cem\u003eInt. J. Dev. Biol.\u003c/em\u003e \u003cb\u003e53\u003c/b\u003e, 1541\u0026ndash;1547 (2009).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLedford, H. Cancer theory faces doubts. \u003cem\u003eNature\u003c/em\u003e \u003cb\u003e472\u003c/b\u003e, 273\u0026ndash;273 (2011).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThompson, E. W. \u0026amp; Newgreen, D. F. Carcinoma Invasion and Metastasis: A Role for Epithelial-Mesenchymal Transition? \u003cem\u003eCancer Res.\u003c/em\u003e \u003cb\u003e65\u003c/b\u003e, 5991\u0026ndash;5995 (2005).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHay, E. D. \u0026amp; Zuk, A. Transformations between epithelium and mesenchyme: Normal, pathological, and experimentally induced. \u003cem\u003eAm. J. Kidney Dis.\u003c/em\u003e \u003cb\u003e26\u003c/b\u003e, 678\u0026ndash;690 (1995).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsai, J. H., Donaher, J. L., Murphy, D. A., Chau, S. \u0026amp; Yang, J. Spatiotemporal Regulation of Epithelial-Mesenchymal Transition is Essential for Squamous Cell Carcinoma Metastasis. (2013).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOca\u0026ntilde;a, O. H. et al. Metastatic Colonization Requires the Repression of the Epithelial-Mesenchymal Transition Inducer Prrx1. \u003cem\u003eCancer Cell.\u003c/em\u003e \u003cb\u003e22\u003c/b\u003e, 709\u0026ndash;724 (2012).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsai, J. H. \u0026amp; Yang J. Epithelial\u0026ndash;mesenchymal plasticity in carcinoma metastasis.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKatsuno, Y., Lamouille, S. \u0026amp; Derynck, R. TGF-b signaling and epithelial\u0026ndash;mesenchymal transition in cancer progression. \u003cb\u003e25\u003c/b\u003e, (2013).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLu, W. \u0026amp; Kang, Y. Epithelial-Mesenchymal Plasticity in Cancer Progression and Metastasis. \u003cem\u003eDev. Cell.\u003c/em\u003e \u003cb\u003e49\u003c/b\u003e, 361\u0026ndash;374 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIser, I. C., Pereira, M. B., Lenz, G. \u0026amp; Wink, M. R. The Epithelial-to‐Mesenchymal Transition‐Like Process in Glioblastoma: An Updated Systematic Review and In Silico Investigation. \u003cem\u003eMed. Res. Rev.\u003c/em\u003e \u003cb\u003e37\u003c/b\u003e, 271\u0026ndash;313 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNing, W. et al. The Prognostic Value of EMT in Glioma and its Role in the Glioma Immune Microenvironment. \u003cem\u003eJ. Mol. Neurosci.\u003c/em\u003e \u003cb\u003e70\u003c/b\u003e, 1501\u0026ndash;1511 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang, Y. et al. BDKRB2 is a novel EMT-related biomarker and predicts poor survival in glioma. \u003cem\u003eAging\u003c/em\u003e \u003cb\u003e13\u003c/b\u003e, 7499\u0026ndash;7516 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKimsa-Dudek, M., Krawczyk, A., Synowiec‐Wojtarowicz, A., Dudek, S. \u0026amp; Pawłowska‐G\u0026oacute;ral, K. The impact of the co‐exposure of melanoma cells to chlorogenic acid and a moderate‐strength static magnetic field. \u003cem\u003eJ. Food Biochem.\u003c/em\u003e \u003cb\u003e44\u003c/b\u003e, (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang, X. et al. An upward 9.4 T static magnetic field inhibits DNA synthesis and increases ROS-P53 to suppress lung cancer growth. \u003cem\u003eTransl Oncol.\u003c/em\u003e \u003cb\u003e14\u003c/b\u003e, 101103 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFan, Z. et al. A Static Magnetic Field Inhibits the Migration and Telomerase Function of Mouse Breast Cancer Cells. \u003cem\u003eBioMed Res. Int.\u003c/em\u003e 1\u0026ndash;9 (2020). (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim, S. C., Im, W., Shim, J. Y., Kim, S. K. \u0026amp; Kim, B. J. Static magnetic field controls cell cycle in cultured human glioblastoma cells. \u003cem\u003eCytotechnology\u003c/em\u003e \u003cb\u003e68\u003c/b\u003e, 2745\u0026ndash;2751 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee, S. H. et al. The Effects of Retinoic Acid and MAPK Inhibitors on Phosphorylation of Smad2/3 Induced by Transforming Growth Factor β1. \u003cem\u003eTuberc Respir Dis.\u003c/em\u003e \u003cb\u003e82\u003c/b\u003e, 42 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim, B. N. et al. TGF-β induced EMT and stemness characteristics are associated with epigenetic regulation in lung cancer. \u003cem\u003eSci. Rep.\u003c/em\u003e \u003cb\u003e10\u003c/b\u003e, 10597 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaminska, B. \u0026amp; Cyranowski, S. Recent Advances in Understanding Mechanisms of TGF Beta Signaling and Its Role in Glioma Pathogenesis. in Glioma Signaling (ed Barańska, J.) vol 1202 179\u0026ndash;201 (Springer International Publishing, Cham, (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiyazono, K., Ehata, S. \u0026amp; Koinuma, D. Tumor-promoting functions of transforming growth factor-β in progression of cancer. \u003cem\u003eUps J. Med. Sci.\u003c/em\u003e \u003cb\u003e117\u003c/b\u003e, 143\u0026ndash;152 (2012).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBirch, J. L. et al. Multifaceted transforming growth factor-beta (TGFβ) signalling in glioblastoma. \u003cem\u003eCell. Signal.\u003c/em\u003e \u003cb\u003e72\u003c/b\u003e, 109638 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAiello, N. M. \u0026amp; Kang, Y. Context-dependent EMT programs in cancer metastasis.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChaffer, C. L. EMT, cell plasticity and metastasis. \u003cem\u003eCancer Metastasis Rev.\u003c/em\u003e (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLoh, C. Y. et al. The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges. \u003cem\u003eCells\u003c/em\u003e \u003cb\u003e8\u003c/b\u003e, 1118 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoomi, M. W., Kalinovsky, T., Rath, M. \u0026amp; Niedzwiecki, A. Modulation of MMP-2 and MMP-9 secretion by cytokines, inducers and inhibitors in human glioblastoma T-98G cells. \u003cem\u003eOncol. Rep.\u003c/em\u003e \u003cb\u003e37\u003c/b\u003e, 1907\u0026ndash;1913 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeng, D. Targeting TGF-β signal transduction for fibrosis and cancer therapy. (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDerynck, R., Turley, S. J. \u0026amp; Akhurst, R. J. TGFβ biology in cancer progression and immunotherapy. \u003cem\u003eNat. Rev. Clin. Oncol.\u003c/em\u003e \u003cb\u003e18\u003c/b\u003e, 9\u0026ndash;34 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRobison, J. G., Pendleton, A. R., Monson, K. O., Murray, B. K. \u0026amp; O\u0026rsquo;Neill, K. L. Decreased DNA repair rates and protection from heat induced apoptosis mediated by electromagnetic field exposure. \u003cem\u003eBioelectromagnetics\u003c/em\u003e \u003cb\u003e23\u003c/b\u003e, 106\u0026ndash;112 (2002).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Glioma, magnetic field, epithelial-mesenchymal transition, TGF-β 1","lastPublishedDoi":"10.21203/rs.3.rs-5377488/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5377488/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eGliomas show suboptimal responses to conventional treatments, with tumor cell migration remaining a formidable challenge in glioma therapy. Epithelial-Mesenchymal Transition (EMT) facilitates invasion of glioma cells, and transforming growth factor β1 serves as a potent factor promoting proliferation, migration, and EMT in glioblastoma (GBM). Magnetic fields have been widely applied in the diagnosis and treatment of various diseases, but their effects on the EMT process in glioma cells remain unclear. In this study, we investigated whether a static magnetic field (SMF) could inhibit EMT and metastasis in glioma cells. Conduct functional analysis using U251 and U87 glioma cell lines. The results indicated that cells treated with TGF-β1 increased invasion and migration capabilities, while showing reduced apoptosis. However, when SMFs were combined with TGF-β1 treatment, there was a notable suppression of cell migration and invasion, accompanied by an increase in apoptosis. Additionally, this combination treatment significantly decreased the protein expression of mesenchymal markers N-cadherin and β-catenin, as well as reduced the levels of the recombinant protein MMP-2. Collectively, these findings suggest that SMFs may reduce glioma cell metastasis by inhibiting EMT. Therefore, SMFs could represent a promising therapeutic strategy for diminishing glioma metastasis.\u003c/p\u003e","manuscriptTitle":"Static magnetic field inhibits Epithelial-Mesenchymal Transition (EMT) and metastasis of glioma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-16 08:56:57","doi":"10.21203/rs.3.rs-5377488/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-12-18T07:08:27+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-16T06:10:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"212168151539603630655130075646911054191","date":"2024-12-11T17:23:08+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-02T09:42:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"26678184719433648944312701908496221272","date":"2024-12-01T06:37:16+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-12-01T02:38:31+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-12-01T02:08:28+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-11-18T17:14:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-11-16T05:02:36+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-11-02T09:23:46+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"47e4bd93-2aaf-477d-805f-9a73d5ee32ea","owner":[],"postedDate":"December 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":41478002,"name":"Biological sciences/Cancer/Cancer therapy"},{"id":41478003,"name":"Biological sciences/Cancer/Cns cancer"},{"id":41478004,"name":"Biological sciences/Cancer/Metastases"},{"id":41478005,"name":"Biological sciences/Cancer/Tumour biomarkers"}],"tags":[],"updatedAt":"2025-04-14T16:08:09+00:00","versionOfRecord":{"articleIdentity":"rs-5377488","link":"https://doi.org/10.1038/s41598-025-96047-x","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-04-11 16:05:06","publishedOnDateReadable":"April 11th, 2025"},"versionCreatedAt":"2024-12-16 08:56:57","video":"","vorDoi":"10.1038/s41598-025-96047-x","vorDoiUrl":"https://doi.org/10.1038/s41598-025-96047-x","workflowStages":[]},"version":"v1","identity":"rs-5377488","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5377488","identity":"rs-5377488","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}