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An in vitro model of ovarian epithelial carcinogenesis: Changes in cell‐cell communication and adhesion occurring during neoplastic progression
Author(s) -
Hoffman Anton G.,
Burghardt Robert C.,
Tilley Roger,
Auersperg Nelly
Publication year - 1993
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910540518
Subject(s) - biology , cell culture , carcinogenesis , epithelium , transfection , cell adhesion , cadherin , microbiology and biotechnology , cell adhesion molecule , malignant transformation , cell–cell interaction , cancer research , cell , pathology , cancer , medicine , genetics
To investigate the cellular mechanisms of ovarian epithelial carcinogenesis, a series of progressively transformed rat ovarian surface epithelial (ROSE) cell lines were developed and studied. Transfection of primary ROSE cells and an immortalized ROSE line (ROSE 199) with the pSV3neo plasmid (SV40 T‐antigen) yielded transformed lines which retained epithelial morphology. In vivo selection of these pSV3neo cell populations resulted in further phenotypic transformation. Transfection of ROSE 199 with pSV2neo/c‐H‐ros EJ (ras EJ p21) resulted in a malignant line which appeared fibroblast‐like and formed invasive sarcomas both in athymic mice and in immunocompetent rats. Gap junctional intercellular communication (GJIC) and cell‐cell adhesion were studied in this series of ROSE lines. Both c‐H‐ras EJ ‐transformation and in vivo selection resulted in a significant reduction of GJIC between adjoining cells and a transition of in vitro migration as continuous epithelial sheets to the dissociation of individual cells. This apparent shift in cell adhesiveness was associated with reduced expression of the E‐cadherin adhesion molecule. Our data suggest that neoplastic progression of the ovarian surface epithelium may be associated with concomitant reductions in GJIC, E‐cadherin expression and functional adhesiveness.