E-cadherin induces mesenchymal-to-epithelial transition in human ovarian surface epithelium

Ovarian carcinomas are thought to arise in the ovarian surface epithelium ( OSE). Although this tissue forms a simple epithelial covering on the ovaria n surface, OSE cells exhibit some mesenchymal characteristics and contain l ittle or no E-cadherin. However, E-cadherin is present in metaplastic OSE c ells that resemble the more complex epithelia of the oviduct, endometrium a nd endocervix, and in primary epithelial ovarian carcinomas. To determine w hether E-cadherin was a cause or consequence of OSE metaplasia, we expresse d this cell-adhesion molecule in simian virus 40-immortalized OSE cells. In these cells the exogenous E-cadherin, all three catenins, and P-actin loca lized at sites of cell-cell contact, indicating the formation of functional adherens junctions. Unlike the parent OSE cell line, which had undergone a typical mesenchymal transformation in culture, E-cadherin expressing cells contained cytokeratins and the tight-junction protein occludin. They also formed cobblestone monolayers in two dimensional culture and simple epithel ia in three-dimensional culture that produced CA125 and shed it into the cu lture medium. CA125 is a normal epithelial-differentiation product of the o viduct, endometrium, and endocervix, but not of normal OSE. It is also a tu mor antigen that is produced by ovarian neoplasms and by metaplastic OSE. T hus, E-cadherin restored some normal characteristics of OSE, such as kerati n, and it also induced epithelial-differentiation markers associated with w eakly preneoplastic, metaplastic OSE and OSE derived primary carcinomas. Th e results suggest an unexpected role for E-cadherin in ovarian neoplastic p rogression.