{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:13:11Z","timestamp":1785413591460,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre","doi-asserted-by":"publisher","award":["2020\/37\/B\/NZ5\/00100"],"award-info":[{"award-number":["2020\/37\/B\/NZ5\/00100"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2020\/37\/B\/NZ5\/00100"],"award-info":[{"award-number":["2020\/37\/B\/NZ5\/00100"]}],"id":[{"id":"https:\/\/ror.org\/03ha2q922","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Recurrence poses a major challenge in epithelial ovarian cancer (EOC), often occurring despite optimal first-line therapy. Dormant cancer cells are believed to play a key role, yet the mechanisms driving their reactivation remain unclear. This study examined whether exosomes released by normal peritoneal mesothelial cells (PMCs) and fibroblasts (PFBs) undergoing iatrogenic senescence after carboplatin and paclitaxel exposure contribute to EOC recurrence. Methods and Results: Senescent PMCs and PFBs secreted markedly more exosomes, identified by CD9, CD63, and CD81, compared with young cells. Exosomes from both cell types more effectively reactivated dormant EOC cells (pEOCs, A2780, OVCAR-3, SKOV-3) than non-exosomal medium constituents. Importantly, senescent PMC-derived exosomes most strongly reactivated pEOCs and SKOV-3, whereas those from senescent PFBs exerted greater effects on pEOCs, OVCAR-3, and SKOV-3. Kinetic studies of exosome internalization revealed that this process was generally more efficient in the presence of exosomes derived from senescent cells compared with those from young donor cells. Compositional analysis revealed distinct profiles between young and senescent exosomes compared in two variants: young PMCs\/senescent PMCs and young PFBs\/senescent PFBS. Senescent PMC exosomes displayed reduced miR-210-3p, miR-409-3p, and miR-421, alongside elevated MMP1, MMP3, and VEGF, while senescent PFB exosomes showed increased amphiregulin and osteopontin but lower MMP1, MMP3, TIMP1, bFGF, VEGF, and HGF. Functionally, senescent PMC exosomes enhanced pEOC migration, invasion, and spheroid formation, and induced the expression of CCL11 and ABCB1. Senescent PFB exosomes promoted migration and upregulated CCL11, TGF-\u03b21, BIRC5, and CHEK1. Conclusions: These findings suggest that therapy-induced senescence in peritoneal cells may contribute to EOC recurrence by reactivating dormant tumor cells through exosomal signaling.<\/jats:p>","DOI":"10.3390\/cancers18091346","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T17:04:59Z","timestamp":1776963899000},"page":"1346","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exosomes Generated by Normal Peritoneal Cells Driven to Senescence by Carboplatin and Paclitaxel Awaken Dormant Ovarian Cancer Cells and Support Their Growth Reinitiation In Vitro"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2194-6770","authenticated-orcid":false,"given":"Szymon","family":"Rutecki","sequence":"first","affiliation":[{"name":"Department of Pathophysiology of Ageing and Civilization Diseases, Pozna\u0144 University of Medical Sciences, \u015awi\u0119cickiego 4 Str., 60-781 Pozna\u0144, Poland"},{"name":"Doctoral School, Poznan University of Medical Sciences, Bukowska 70 Str., 60-812 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7999-4083","authenticated-orcid":false,"given":"Adrianna","family":"Krawiec","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology of Ageing and Civilization Diseases, Pozna\u0144 University of Medical Sciences, \u015awi\u0119cickiego 4 Str., 60-781 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5585-1968","authenticated-orcid":false,"given":"Agnieszka","family":"Le\u015bniewska-Bocianowska","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology of Ageing and Civilization Diseases, Pozna\u0144 University of Medical Sciences, \u015awi\u0119cickiego 4 Str., 60-781 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Matuszewska","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology of Ageing and Civilization Diseases, Pozna\u0144 University of Medical Sciences, \u015awi\u0119cickiego 4 Str., 60-781 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eryk","family":"Naumowicz","sequence":"additional","affiliation":[{"name":"General Surgery Ward, Medical Centre HCP, 28 Czerwca 1956 r. 223\/229 Str., 61-485 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3313-7188","authenticated-orcid":false,"given":"Sebastian","family":"Szubert","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Division of Gynecologic Oncology, Poznan University of Medical Sciences, Polna 33 Str., 60-535 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Ksi\u0105\u017cek","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, Prince Mieszko I Poznan Medical University of Applied Sciences, Bu\u0142garska 55 Str., 60-320 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8267-5428","authenticated-orcid":false,"given":"Justyna","family":"Miku\u0142a-Pietrasik","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology of Ageing and Civilization Diseases, Pozna\u0144 University of Medical Sciences, \u015awi\u0119cickiego 4 Str., 60-781 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"International Collaborative Ovarian Neoplasm Group (2002). 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