Chronic exposure of cultured transformed mouse epidermal cells to transforming growth factor-β1 induces an epithelial-mesenchymal transdifferentiation and a spindle tumoral phenotype

C. Caulin, F. G. Scholl, P. Frontelo, C. Gamallo, M. Quintanilla

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

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 languageEnglish (US)
Pages (from-to)1027-1035
Number of pages9
JournalCell Growth and Differentiation
Volume6
Issue number8
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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