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

202 Citations (Scopus)

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

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Epithelial-Mesenchymal Transition
Cadherins
Epithelium
Oviducts
Keratins
Endometrium
Carcinoma
Occludin
Tight Junction Proteins
Adherens Junctions
Catenins
Simian virus 40
Differentiation Antigens
Metaplasia
Cell Adhesion Molecules
Neoplasm Antigens
Ovarian Neoplasms
Culture Media
Actins

ASJC Scopus subject areas

  • General

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E-cadherin induces mesenchymal-to-epithelial transition in human ovarian surface epithelium. / Auersperg, Nelly; Pan, Jie; Grove, Bryon D.; Peterson, Todd; Fisher, Janet; Maines-Bandiera, Sarah; Somasiri, Aruna; Roskelley, Calvin D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 11, 25.05.1999, p. 6249-6254.

Research output: Contribution to journalArticle

Auersperg, Nelly ; Pan, Jie ; Grove, Bryon D. ; Peterson, Todd ; Fisher, Janet ; Maines-Bandiera, Sarah ; Somasiri, Aruna ; Roskelley, Calvin D. / E-cadherin induces mesenchymal-to-epithelial transition in human ovarian surface epithelium. In: Proceedings of the National Academy of Sciences of the United States of America. 1999 ; Vol. 96, No. 11. pp. 6249-6254.
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