A new class of extracellular vesicles, Motile Vesicles (“MoVes”), carry whole genome DNA and are emitted during active cancer cell migration

A new class of extracellular vesicles, Motile Vesicles (“MoVes”), carry whole genome DNA and are emitted during active cancer cell migration | 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 A new class of extracellular vesicles, Motile Vesicles (“MoVes”), carry whole genome DNA and are emitted during active cancer cell migration Julia Burnier, Thupten Tsering, Amélie Nadeau, Masoud Ghasemi, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7054528/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Migrating cancer cells emit a diverse array of extracellular vesicles (EVs) that carry bioactive molecules, including DNA, which may mediate intercellular communication and metastatic progression. However, the mechanisms and biological significance of DNA packaging in EVs remain poorly understood. Here, we identify and characterize a novel class of large EVs (2–5 μm), termed Motile Vesicles (MoVes), which are selectively released during cancer cell migration and closely associated with epithelial–mesenchymal transition (EMT). Using scanning electron microscopy and live-cell imaging, we show that MoVes are actively shed by cancer cells—a phenomenon absent in normal epithelial cells. Whole-genome sequencing reveals that MoVes encapsulate the full genomic content of their parent cells, faithfully reflecting their mutational landscape. Proteomic profiling further distinguishes MoVes from other EV subtypes, with FAM3C—an interleukin-like EMT inducer—emerging as a specific molecular marker. These findings define MoVes as a cancer-specific EV population that carries genomic DNA during EMT and migration, unveiling new insights into extracellular DNA biology and potential mechanisms of cancer progression and metastatic dissemination. Biological sciences/Cell biology/Cell migration/Epithelial–mesenchymal transition Biological sciences/Cancer Extracellular vesicles Motile Vesicles epithelial-mesenchymal transition migration FAM3C WGS extracellular vesicles associated DNA Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supplementarytable2.xlsx Supplementary Table 2 SupplementaryVideo3bMDAMB231tgfbeta1inhibitor.mov Supplementary Video 3b SupplementaryVideolegends.docx Supplementary Video legends SupplementaryVideo4MCF10AwithEMTrep2.mov Supplementary Video 4 Supplementarytable3.xlsx Supplementary Table 3 SupplementaryVideo1amcf10AT.mp4 Supplementary Video 1a SupplementaryTable1.xlsx Supplementary Table 1 SupplementaryVideo3a4T1tgfb1receptorinhibitor150nm.mov Supplementary Video 3a ExtendedDataFigures.docx Extended/Supplementary Figures SupplementaryVideo2NCM.mp4 Supplementary Video 2 SupplementaryVideo1fMCF10A.mp4 Supplementary Video 1f SupplementaryVideo1b4t1.mp4 Supplementary Video 1b SupplementaryVideo1c4T1migrasome1copy.mov Supplementary Video 1c SupplementaryVideo1emdamb231migrasome1.mp4 Supplementary Video 1e SupplementaryVideo1dMDAMB231.mp4 Supplementary Video 1d Cite Share Download PDF Status: Under Review 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-7054528","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":487065535,"identity":"bea1f7f7-8bb3-4986-8f53-12de15033517","order_by":0,"name":"Julia 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migration","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Extracellular vesicles, Motile Vesicles, epithelial-mesenchymal transition, migration, FAM3C, WGS, extracellular vesicles associated DNA","lastPublishedDoi":"10.21203/rs.3.rs-7054528/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7054528/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Migrating cancer cells emit a diverse array of extracellular vesicles (EVs) that carry bioactive molecules, including DNA, which may mediate intercellular communication and metastatic progression. However, the mechanisms and biological significance of DNA packaging in EVs remain poorly understood. Here, we identify and characterize a novel class of large EVs (2–5 μm), termed Motile Vesicles (MoVes), which are selectively released during cancer cell migration and closely associated with epithelial–mesenchymal transition (EMT). Using scanning electron microscopy and live-cell imaging, we show that MoVes are actively shed by cancer cells—a phenomenon absent in normal epithelial cells. Whole-genome sequencing reveals that MoVes encapsulate the full genomic content of their parent cells, faithfully reflecting their mutational landscape. Proteomic profiling further distinguishes MoVes from other EV subtypes, with FAM3C—an interleukin-like EMT inducer—emerging as a specific molecular marker. These findings define MoVes as a cancer-specific EV population that carries genomic DNA during EMT and migration, unveiling new insights into extracellular DNA biology and potential mechanisms of cancer progression and metastatic dissemination.","manuscriptTitle":"A new class of extracellular vesicles, Motile Vesicles (“MoVes”), carry whole genome DNA and are emitted during active cancer cell migration","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-21 03:35:33","doi":"10.21203/rs.3.rs-7054528/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-cell-biology","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"ncb","sideBox":"Learn more about [Nature Cell Biology](http://www.nature.com/ncb/)","snPcode":"","submissionUrl":"","title":"Nature Cell Biology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Research","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"98da5526-3022-4ca9-bf59-b0a287127caa","owner":[],"postedDate":"July 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":51712607,"name":"Biological sciences/Cell biology/Cell migration/Epithelial\u0026#x2013;mesenchymal transition"},{"id":51712608,"name":"Biological sciences/Cancer"}],"tags":[],"updatedAt":"2026-04-14T19:15:51+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-21 03:35:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7054528","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7054528","identity":"rs-7054528","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}