Effects of Metformin on Bone-derived Mesenchymal Stromal Cell–breast Cancer Cell Line Interactions

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This preprint investigates how metformin influences interactions between human bone-derived mesenchymal stromal cells and four breast cancer cell lines. The study found that while metformin inhibited the proliferation of the stromal cells, it also altered their conditioned media to significantly impair the migration of specific aggressive breast cancer cell lines like MDA-MB-231 and MDA-MB-436. These effects were associated with changes in adipokine expression that suggested increased osteogenic signaling and potential metastasis impairment. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Metformin is used to treat patients with diabetes mellitus and that was found to lower the incidence of cancer. The present study investigated the effects of metformin on human bone-derived mesenchymal stromal cells (BM-MSC) and their breast cancer cell line interactions. BM-MSCs were tested for growth stimulation and migration controlling activity on four breast cancer cell lines employing MTT tests, migration scratch tests and assays of the expression of adipokines in Western Blot arrays. Compared to breast cancer cell lines, metformin significantly inhibited the proliferation of BM-MSC lines. Pretreatment of BM-MSCs with metformin showed variable effects on breast cancer cell lines depending on the specific BM-MSC cancer line combination. Metformin significantly impaired the migration of MDA-MB-231 and MDA-MB-436 in response to conditioned media (CM) of drug pretreated BM-MSCs. Metformin-induced alterations of adipokines by BM-MSC CM indicated increased osteogenic signaling and possibly impairment of metastasis. The anticancer activities of metformin seem to be the result of direct and indirect mechanisms. A lower metformin-induced protumor activity of BM-MSCs in the bone microenvironment seem to contribute to the anticancer effects of this drug in breast cancer patients.
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Effects of Metformin on Bone-derived Mesenchymal Stromal Cell–breast Cancer Cell Line Interactions | 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effects of Metformin on Bone-derived Mesenchymal Stromal Cell–breast Cancer Cell Line Interactions Maryana Teufelsbauer, Clemens Lang, Adelina Plangger, barbara Rath, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-754543/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Metformin is used to treat patients with diabetes mellitus and that was found to lower the incidence of cancer. The present study investigated the effects of metformin on human bone-derived mesenchymal stromal cells (BM-MSC) and their breast cancer cell line interactions. BM-MSCs were tested for growth stimulation and migration controlling activity on four breast cancer cell lines employing MTT tests, migration scratch tests and assays of the expression of adipokines in Western Blot arrays. Compared to breast cancer cell lines, metformin significantly inhibited the proliferation of BM-MSC lines. Pretreatment of BM-MSCs with metformin showed variable effects on breast cancer cell lines depending on the specific BM-MSC cancer line combination. Metformin significantly impaired the migration of MDA-MB-231 and MDA-MB-436 in response to conditioned media (CM) of drug pretreated BM-MSCs. Metformin-induced alterations of adipokines by BM-MSC CM indicated increased osteogenic signaling and possibly impairment of metastasis. The anticancer activities of metformin seem to be the result of direct and indirect mechanisms. A lower metformin-induced protumor activity of BM-MSCs in the bone microenvironment seem to contribute to the anticancer effects of this drug in breast cancer patients. Cancer Biology Breast cancer Metformin bone-derived mesenchymal stromal cells migration assay adipokines Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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 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-754543","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":43684366,"identity":"15966ff8-e808-4123-95f6-90b48268f91b","order_by":0,"name":"Maryana Teufelsbauer","email":"","orcid":"","institution":"Medical University of Vienna","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Maryana","middleName":"","lastName":"Teufelsbauer","suffix":""},{"id":43684367,"identity":"276aeed4-97e6-4257-a53e-e723c4b06780","order_by":1,"name":"Clemens Lang","email":"","orcid":"","institution":"Medical University of 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