TENASCIN-X EXPRESSION IN TUMOR-CELLS AND FIBROBLASTS - GLUCOCORTICOIDS AS NEGATIVE REGULATORS IN FIBROBLASTS

Tenascin-X has recently been shown to be a novel member of the tenasci n 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 apparen t molecular mass of similar to 450 kDa, In addition fibroblasts contai ned a major tenascin-X isoform of 220 kDa. On northern blots, a single major transcript with a size of similar to 13 kb was detected. No ove rexpression of tenascin-X protein was found in primary fibroblasts of the tenascin-C-gene knockout mice, Steroid hormone glucocorticoids, we re 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 expres sion level of tenascin-X, As in vivo study, carcinoma cells were trans planted into nude mice. In contrast to the ubiquitous presence of tena scin-X in adult skin, expression of tenascin-X protein during tumorige nesis was found to be downregulated considerably not only in tumor cel ls themselves but also in tumor stroma, These findings provide evidenc e that the expression of tenascin-X can be influenced by stromal-epith elial interactions, We have identified glucocorticoids as physiologica l inhibitors of tenascin-X and suggest that glucocorticoids mag in par t participate in the downregulation of tenascin-X in fibroblasts in vi vo.