Transformed mouse epidermal keratinocytes of the cell line PDV, when cultured under the presence of transforming growth factor-β1 (TGF-β1), escaped the block of growth exerted by this factor in normal keratinocytes and underwent marked changes in cell differentiation. TGF-β1 induced disruption of epithelial interactions, dispersion of cells, increased local movement, and conversion to a fibroblast-like morphology. These changes were reversible and correlated with down-regulation of epithelial protein markers such as E-cadherin and cytokeratins and up-regulation of vimentin, TGF-β1- treated cells with a fibroblast-like phenotype induced spindle cell carcinomas upon transplantation in athymic nude mice, whereas untreated PDV cells or fusiform cells reverted to the epithelial phenotype and produced well-differentiated squamous cell carcinomas. Nontumorigenic immortalized epidermal keratinocytes, when grown under the presence of TGF-β1, did not transdifferentiate to a mesenchymal phenotype, their proliferation was blocked, and cells finally died. These results suggest a role for TGF-β1 in the progression of squamous carcinoma cells to spindle carcinomas in mouse skin carcinogenesis.
|Original language||English (US)|
|Number of pages||9|
|Journal||Cell Growth and Differentiation|
|State||Published - 1995|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology