Tenascin-X expression in tumor cells and fibroblasts: glucocorticoids as negative regulators in fibroblasts

Abstract

Tenascin-X has recently been shown to be a novel member of the tenascin family and its distribution is often reciprocal to that of tenascin-C in the developing mouse embryo. We have investigated the expression of tenascin-X in fibroblasts and carcinoma cells in culture. Tenascin-X protein was secreted in vitro in the conditioned media at an apparent molecular mass of approximately 450 kDa. In addition fibroblasts contained a major tenascin-X isoform of 220 kDa. On northern blots, a single major transcript with a size of approximately 13 kb was detected. No overexpression of tenascin-X protein was found in primary fibroblasts of the tenascin-C-gene knockout mice. Steroid hormone glucocorticoids, were found to downregulate tenascin-X mRNA levels and protein synthesis in fibroblasts but not carcinoma cells at physiological concentrations. None of the growth factors or cytokines examined affected the expression level of tenascin-X. As in vivo study, carcinoma cells were transplanted into nude mice. In contrast to the ubiquitous presence of tenascin-X in adult skin, expression of tenascin-X protein during tumorigenesis was found to be down-regulated considerably not only in tumor cells themselves but also in tumor stroma. These findings provide evidence that the expression of tenascin-X can be influenced by stromal-epithelial interactions. We have identified glucocorticoids as physiological inhibitors of tenascin-X and suggest that glucocorticoids may in part participate in the downregulation of tenascin-X in fibroblasts in vivo.