TENASCIN-C INDUCTION BY THE DIFFUSIBLE FACTOR EPIDERMAL GROWTH-FACTORIN STROMAL-EPITHELIAL INTERACTIONS

Tenascin-C, a six-armed extracellular matrix glycoprotein, is expresse d in a temporally and spatially restricted pattern during carcinogenes is and invasion or metastasis of carcinoma cells in association with s tromal-epithelial interactions. The human epidermoid carcinoma-derived cell lines, A431 and HEp-2, which do not express tenascin-C by themse lves in vitro, do express tenascin-C after transplantation into nude m ice, and transforming growth factor beta 1 (TCF-beta 1) induces them t o express tenascin-C in vitro. Epidermal growth factor(EGF) induced te nascin-C in these cells more effectively (about 3.5-fold greater) than did TGF-beta 1 Hepatocyte growth factor (HCF) and platelet-derived gr owth factor (PDGF) had little effect on the induction of tenascin-C. E GF also induced other extracellular matrix components, fibronectin and laminin. Tenascin-C was also induced when the carcinoma cells were co -cultured with embryonic fibroblasts from mice which were homozygous f or a null mutation in the tenascin-C gene, or when the conditioned med ium from these cells was added. The induction of tenascin-C in the co- culture was reduced by treating the cells with antibodies against EGF or its receptor. The addition of EGF caused both cell types to disrupt their cytoskeleton and focal contacts as evidenced by the loss of str ess fibers and vinculin plaques. EGF did neither induce tenascin-C nor affect the morphology in tenascin-C-nonproducing A549 carcinoma cells , which did not produce tenascin-C after transplantation. Thus, EGF in duces tenascin-C in tenascin-C-nonproducing human carcinoma cells thro ugh EGF receptors. Furthermore, in stromal-epithelial interactions, th e diffusible factor EGF participates in the induction of human tenasci n-C in these cells through EGF receptors. (C) 1995 Wiley-Liss, Inc.