PT  - JOURNAL ARTICLE
AU  - Wang, Liang-Yuan
AU  - Hsu, Che-Fang
AU  - Chu, Tang-Yuan
TI  - 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
AID  - 10.1136/ijgc-2023-IGCS.382
DP  - 2023 Nov 01
TA  - International Journal of Gynecologic Cancer
PG  - A209--A209
VI  - 33
IP  - Suppl 4
4099  - http://ijgc.bmj.com/content/33/Suppl_4/A209.2.short
4100  - http://ijgc.bmj.com/content/33/Suppl_4/A209.2.full
SO  - Int J Gynecol Cancer2023 Nov 01; 33
AB  - Introduction Previously, 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.Methods Partially 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.Results Cell 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/Implications The 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.