RT Journal Article
SR Electronic
T1 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
JF International Journal of Gynecologic Cancer
JO Int J Gynecol Cancer
FD BMJ Publishing Group Ltd
SP A209
OP A209
DO 10.1136/ijgc-2023-IGCS.382
VO 33
IS Suppl 4
A1 Wang, Liang-Yuan
A1 Hsu, Che-Fang
A1 Chu, Tang-Yuan
YR 2023
UL http://ijgc.bmj.com/content/33/Suppl_4/A209.2.abstract
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.