Chronic exposure of cultured transformed mouse epidermal cells to transforming growth factor-beta 1 induces an epithelial-mesenchymal transdifferentiation and a spindle tumoral phenotype.
Transformed mouse epidermal keratinocytes of the cell line PDV, when cultured under the presence of transforming growth factor-beta 1 (TGF-beta 1), escaped the block of growth exerted by this factor in normal keratinocytes and underwent marked changes in cell differentiation. TGF-beta 1 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 upregulation of vimentin. TGF-beta 1-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-beta 1, did not transdifferentiate to a mesenchymal phenotype, their proliferation was blocked, and cells finally died. These results suggest a role of TGF-beta 1 in the progression of squamous carcinoma cells to spindle carcinomas in mouse skin carcinogenesis.
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Cientificas-Universidad Autonoma de Madrid, Spain.
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Caulín
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Scholl
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Frontelo
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Gamallo
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Quintanilla
D000818:Animals; D015415:Biomarkers / Q000737:chemistry; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002461:Cell Line, Transformed; D002908:Chronic Disease; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D007267:Injections; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008819:Mice, Nude; D010641:Phenotype; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D015415:Biomarkers; D016212:Transforming Growth Factor beta