Fig. 2.

EMT events in ovarian cancer metastasis. In step 1. FTSECs in the fallopian tube develop STIC lesions with characteristic alterations in TP53 that develop into HGS cancers in the fallopian tube and the ovaries. Epithelial ovarian cancer (EOC) cells detach and shed into the peritoneal fluid for transcoelomic spread or enter the blood vessels leading to hematogenous metastasis. In Step 2, shed EOCs in the ascites retain epithelial characteristics, undergo EMT, or acquire mesenchymal characteristics, or enter a partial E/M state, forming anoikis resistant cell aggregates. Ascites flow facilitates aggregate attachment and spread throughout the peritoneal cavity leading to cell aggregate ‘adhesions’ to the peritoneal membrane that covers the visceral organs and pelvic and abdominal cavities. Such adhesions in Step 3 can undergo MET (reverse EMT) to acquire an epithelial phenotype enabling the cells to establish and grow at secondary sites including at the omentum. At the peritoneal interface, cancer cells invade PMCs facilitated by integrins and TGFβ, developing secondary tumors and metastasis. FTSEC - fallopian tube secretory epithelial cells, STIC - serous tubal intraepithelial carcinoma, HGSC - high grade serous cancer, EOC - epithelial ovarian cancer, MET - Mesenchymal to epithelial transition, PMCs - peritoneal mesothelial cells, TGFβ - Transforming growth factor-β