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

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

^*Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC Canada V6H 3V5; ^†Department of Anatomy, University of British Columbia, Vancouver, BC Canada V6T 1Z3; and ^‡Department of Anatomy and Cell Biology, University of North Dakota, Grand Forks, ND 58202

Edited by M. Judah Folkman, Harvard Medical School, Brookline, MA, and approved March 30, 1999 (received for review September 23, 1998)

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.

Footnotes

↵ § To whom reprint requests should be addressed at: Department of Anatomy, University of British Columbia, 2177 Wesbrook Mall, Vancouver, BC Canada V6T 1Z3. e-mail: roskelly{at}unixg.ubc.ca.
This paper was submitted directly (Track II) to the Proceedings Office.
ABBREVIATIONS:

CK,

cytokeratins;

OSE,

ovarian surface epithelium