An ovarian adenocarcinoma line derived from SV40/E-cadherin-transfected normal human ovarian surface epithelium.
Epithelial ovarian carcinomas are thought to originate in the ovarian surface epithelium (OSE), i.e., the mesothelium covering the ovary, but experimental evidence for this origin has been lacking. Contrary to most epithelia, where neoplastic progression is associated with a reduction of E-cadherin, this cell-cell adhesion molecule is sparse in normal human OSE but its expression increases with the development of ovarian epithelial metaplasia and neoplasia. Concurrently, the tumors tend to acquire characteristics of the complex epithelia of the oviduct and uterus. The high proportion of ovarian cancers where such aberrant Mullerian differentiation occurs suggests that this change may confer a selective advantage on the transforming cells. We previously demonstrated that increased E-cadherin expression may be a cause, rather than a consequence, of such Mullerian differentiation. E-cadherin was transfected into SV40 large T antigen-immortalized, E-cadherin-negative cells derived from normal OSE. Constitutive expression of E-cadherin re-established normal epithelial markers that had been lost in culture, such as keratin, and induced markers of metaplasia and neoplasia, such as CA125. In the present study, SV40-immortalized, E-cadherin-transfected cells, but not the E-cadherin-negative controls, were found to be anchorage-independent and to form transplantable, invasive s.c. and i.p. adenocarcinomas in 100% of injected SCID mice. Tumor cells injected i.p. seeded the mesenteries and omentum, invaded the liver and thigh musculature and produced ascites. The presence of SV40 large T antigen in the tumor cell nuclei confirmed their origin as transfected OSE cells. Our results demonstrate that ovarian adenocarcinomas can be derived by genetic manipulation of normal human OSE.
Ong
A
A
Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada.
Maines-Bandiera
S L
SL
Roskelley
C D
CD
Auersperg
N
N
D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism*; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016513:Mice, SCID; D018200:Mixed Tumor, Mullerian / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000952:Antigens, Polyomavirus Transforming; D015820:Cadherins