EP319/#1479  Ovulation releases fibronectin to promote peritoneal seeding of precancerous and cancerous high-grade serous carcinoma cells originating from the fallopian tube epithelium through integrin Β1 signaling

• Published in: International journal of gynecological cancer Vol. 33; no. Suppl 4; p. A209
• Main Authors: Wang, Liang-Yuan, Hsu, Che-Fang, Chu, Tang-Yuan
• Format: Journal Article
• Language: English
• Published: Kidlington BMJ Publishing Group Ltd 01.11.2023; Elsevier Inc; Elsevier Limited
• Subjects: Cell growth; ePoster Viewing; Fallopian tubes
• ISSN: 1048-891X; 1525-1438
• DOI: 10.1136/ijgc-2023-IGCS.382

IntroductionPreviously, we have discovered ovulatory follicular fluid (FF) carries transforming signals to promote full-course carcinogenesis of fallopian tube epithelium (FTE), the origin of ovarian high-grade serous carcinoma[https://pubmed.ncbi.nlm.nih.gov/33530497/]. This study investigated FF-fibronectin(FN) in peritoneal seeding of transforming FTE cells.MethodsPartially and fully transformed FTE cells were treated with FF, paired peritoneal fluid (PF), or recombinant FN. Transformation phenotypes were evaluated in FTE cells with/without ITGB1 knock-down. Peritoneal seeding was evaluated by IVIS after i.p. xenograft together with FF in NSG mice.ResultsCell migration-promoting activity was observed after treating with >100-KDa FF or FN protein which was three times higher in FF than in the paired PF. Compared to the full-transformation activity of FF, FN specifically promoted cell proliferation, migration, or invasion. ITGB1- KD caused lower cell proliferation, peritoneal attachment, and AIG. It also reduced the migration-and proliferation-promoting effects of FF and FN. Compared to FF treatment which generally increased p-FAK, p-SRC, p-ERK, and p-AKT, FN treatment increased p-FAK and p-SRC. Looking into the changes in FF- and FN-treated cells, ITGB1-KD resulted in a decrease of p-ERK, p-SRC, or p-FAK and an increase of p-AKT. In the mouse i.p. xenograft tumorigenesis model, depletion of FN from FF showed in a marked reduction of intraperitoneal seedings at week 7, and ITGB1-KD resulted in a decrease at day 12.Conclusion/ImplicationsThe results disclose proliferation-, migration- and invasion-promoting activities of FN abundantly present in ovulatory FF, which promotes peritoneal seedings of transformed FTE cells. Integrin β1 primarily mediates this activity.