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 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.
Auersperg
N
N
Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC Canada V6H 3V5.
Pan
J
J
Grove
B D
BD
Peterson
T
T
Fisher
J
J
Maines-Bandiera
S
S
Somasiri
A
A
Roskelley
C D
CD
D000199:Actins / Q000032:analysis; D015820:Cadherins / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D003598:Cytoskeletal Proteins / Q000032:analysis; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D007633:Keratins / Q000096:biosynthesis; D008648:Mesoderm / Q000166:cytology*; D008679:Metaplasia; D010053:Ovary / Q000166:cytology*; D013539:Simian virus 40
D000199:Actins; D015820:Cadherins; D003598:Cytoskeletal Proteins; D007633:Keratins