{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T18:23:12Z","timestamp":1779906192147,"version":"3.53.1"},"reference-count":53,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:00:00Z","timestamp":1721865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Council, Taiwan","award":["107-2314-B-281-005-MY3"],"award-info":[{"award-number":["107-2314-B-281-005-MY3"]}]},{"name":"National Science Council, Taiwan","award":["111-2314-B-281-008-MY3"],"award-info":[{"award-number":["111-2314-B-281-008-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Our study explores the role of cancer-derived extracellular exosomes (EXs), particularly focusing on collagen alpha-3 (VI; COL6A3), in facilitating tumor dissemination and metastasis in epithelial ovarian cancer (EOC). We found that COL6A3 is expressed in aggressive ES2 derivatives, SKOV3 overexpressing COL6A3 (SKOV3\/COL6A3), and mesenchymal-type ovarian carcinoma stromal progenitor cells (MSC-OCSPCs), as well as their EXs, but not in less aggressive SKOV3 cells or ES2 cells with COL6A3 knockdown (ES2\/shCOL6A3). High COL6A3 expression correlates with worse overall survival among EOC patients, as evidenced by TCGA and GEO data analysis. In vitro experiments showed that EXs from MSC-OCSPCs or SKOV3\/COL6A3 cells significantly enhance invasion ability in ES2 or SKOV3\/COL6A3 cells, respectively (both, p &lt;0.001). In contrast, ES2 cells with ES2\/shCOL6A3 EXs exhibited reduced invasion ability (p &lt; 0.001). In vivo, the average disseminated tumor numbers in the peritoneal cavity were significantly greater in mice receiving intraperitoneally injected SKOV3\/COL6A3 cells than in SKOV3 cells (p &lt; 0.001). Furthermore, mice intravenously (IV) injected with SKOV3\/COL6A3 cells and SKOV3\/COL6A3-EXs showed increased lung colonization compared to mice injected with SKOV3 cells and PBS (p = 0.007) or SKOV3\/COL6A3 cells and PBS (p = 0.039). Knockdown of COL6A3 or treatment with EX inhibitor GW4869 or rapamycin-abolished COL6A3-EXs may suppress the aggressiveness of EOC.<\/jats:p>","DOI":"10.3390\/ijms25158121","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T11:43:44Z","timestamp":1721907824000},"page":"8121","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["COL6A3 Exosomes Promote Tumor Dissemination and Metastasis in Epithelial Ovarian Cancer"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0634-0439","authenticated-orcid":false,"given":"Chih-Ming","family":"Ho","sequence":"first","affiliation":[{"name":"Gynecologic Cancer Center, Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei 106, Taiwan"},{"name":"School of Medicine, Fu Jen Catholic University, Hsinchuang, New Taipei City 242, Taiwan"},{"name":"Department of Medical Research, Cathay General Hospital, Sijhih, New Taipei City 221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1454-0521","authenticated-orcid":false,"given":"Ting-Lin","family":"Yen","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Cathay General Hospital, Sijhih, New Taipei City 221, Taiwan"},{"name":"School of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7011-3754","authenticated-orcid":false,"given":"Tzu-Hao","family":"Chang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Hung","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cathay General Hospital, Taipei 106, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer statistics, 2019","volume":"69","author":"Siegel","year":"2019","journal-title":"CA Cancer J. 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