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American Journal of Pathology, Vol 145, 846-855, Copyright © 1994 by American Society for Investigative Pathology

REGULAR ARTICLES

Dermal fibroblasts tumor suppression of ras-transformed keratinocytes is associated with induction of squamous cell differentiation

S Ramon y Cajal, C Missero, E Marchetti and GP Dotto
Department of Pathological Anatomy, Clinic Puerta de Hierro, Madrid, Spain.

We have previously reported that tumor formation of ras-transformed keratinocytes can be suppressed by dermal fibroblasts through production of a diffusible growth inhibitory factor of the transforming growth factor-beta (TGF-beta) family. Keratinocytes transformed by ras and E1a oncogenes or papilloma-derived keratinocytes transformed by a ras oncogene show concomitant resistance to dermal fibroblast tumor suppression and TGF-beta growth inhibition. We report here that dermal fibroblast tumor suppression is associated with a striking induction of squamous cell differentiation and that this effect is blocked in tumors resistant to dermal fibroblast inhibition. This experimental system strongly supports the notion that suppression of tumorigenicity and induction of a differentiated phenotype are closely associated events.


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Copyright © 1994 by the American Society for Investigative Pathology.