Cancer associated fibroblast drives spheroid formation and pleural dissemination in non-small cell lung cancer

Cancer associated fibroblast drives spheroid formation and pleural dissemination in non-small cell lung cancer | 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 Cancer associated fibroblast drives spheroid formation and pleural dissemination in non-small cell lung cancer Naoki Matsuda, Ken Suzawa, Yin Min Thu, Shuta Tomida, Tomoaki Higashihara, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6239941/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 Pleural dissemination in non-small cell lung cancer (NSCLC) refers to cancer cells directly spreading from the primary tumor to the extrapulmonary thoracic cavity, where they colonize the pleura. This study investigated the impact of cancer-associated fibroblasts (CAFs) on the development of pleural dissemination in NSCLC. Using in vitro coculture and in vivo pleural dissemination models, we found that CAFs led to pleural dissemination by promoting cancer cell migration, anchorage-independent growth, adhesion, invasion, and spheroid formation. RNA-seq analysis revealed that CAFs upregulated the expression of the matricellular protein cellular communication network factor 1 (CCN1) in cancer cells. Subsequently, we confirmed that CCN1-overexpressing lung cancer cell lines exhibited enhanced migratory and adhesive properties in vitro and increased tumorigenicity in the thoracic cavity in the mouse model of pleural dissemination. These findings demonstrated that CAFs drive pleural dissemination by inducing spheroid formation and upregulating CCN1 expression in NSCLC. Biological sciences/Cancer Biological sciences/Cell biology cancer associated fibroblast lung cancer pleural dissemination CCN1 Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryFigure1.pdf 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 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-6239941","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":447166484,"identity":"2a27f581-29d8-41ad-aed3-c467b2384936","order_by":0,"name":"Naoki Matsuda","email":"","orcid":"","institution":"Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Naoki","middleName":"","lastName":"Matsuda","suffix":""},{"id":447166485,"identity":"ed92bf32-155d-45ad-bdf9-761292c24b8b","order_by":1,"name":"Ken 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