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

Nelly Auersperg, Jie Pan, Bryon D. Grove, Todd Peterson, Janet Fisher, Sarah Maines-Bandiera, Aruna Somasiri, Calvin D. Roskelley

Research output: Contribution to journalArticle

204 Scopus citations

Abstract

Ovarian carcinomas are thought to arise in the ovarian surface epithelium (OSE). Although this tissue forms a simple epithelial covering on the ovarian surface, OSE cells exhibit some mesenchymal characteristics and contain little or no E-cadherin. However, E-cadherin is present in metaplastic OSE cells that resemble the more complex epithelia of the oviduct, endometrium and endocervix, and in primary epithelial ovarian carcinomas. To determine whether E-cadherin was a cause or consequence of OSE metaplasia, we expressed this cell-adhesion molecule in simian virus 40- immortalized OSE cells. In these cells the exogenous E-cadherin, all three catenins, and F-actin localized 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 epithelia in three-dimensional culture that produced CA125 and shed it into the culture medium. CA125 is a normal epithelial- differentiation product of the oviduct, endometrium, and endocervix, but not of normal OSE. It is also a tumor antigen that is produced by ovarian neoplasms and by metaplastic OSE. Thus, E-cadherin restored some normal characteristics of OSE, such as keratin, and it also induced epithelial- differentiation markers associated with weakly preneoplastic, metaplastic OSE and OSE-derived primary carcinomas. The results suggest an unexpected role for E-cadherin in ovarian neoplastic progression.

Original languageEnglish (US)
Pages (from-to)6249-6254
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number11
DOIs
StatePublished - May 25 1999
Externally publishedYes

ASJC Scopus subject areas

  • General

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