Studies on extracellular matrix tenascin family

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Tenascins are a family of large multimeric extracellular matrix proteins. The family is comprised of at least five members of related proteins in vertebrated : the original tenascin (tenascin-C,TNC), tenascin-R (TNR), tenascin-X (TNX), recent discoverd tenascin-Y (TNY), and tenascin-W (TNW). Especially, we were involved in the discovery of TNX and was the first toidentify TNX on the protein level. In this study, we attempted to reveal the interrelationship among the tenascin family members. In particular, we have disclosed three new findings as follows. First, we examined the expression patterns of TNX and TNC to reveal whether their expression is changed in proportion to the grade of malignancy. Expression of TNX was up-regulated to a higher degree in low-grade astrocytomas than in high-tfade astrocytomas. In contrast, TNC was more strongly expressed in the intercellular spaces and in tumor vessels in high-grade astrocytomas than in low-grade astrocytomas. In the tissues expressing bo … More th TNs, the distribution of TNX was often reciprocal to that of TNC.Second, glucocorticoids were found to downregulate TNX mRNA levels and protein synthesis in fibroblasts. As in vivo study, carcinoma cells were transplanted into nude mice. In contrast to the ubiqutious presence of TNX in adult skin, expression of TNX protein during tumorigenesis was found to be down-regulated considerably not only in tumor cells themsclves but also in tumor stroma. These findings provide evidence that the expression of TNX can be influenced by stromal-epithelial interactions. We have identified glucocorticoids as physiological inhibitors of TNX and suggest that glucocorticoids may in part partcipate in the downregulation of TNX in fibroblast in vivo. Third, we determined a total of 67,977-bp sepuence including the mouse TNX loci. The deduced amino acid sequence (4,114 residues) reveals that mouse TNX has the characteristic primary structure, which begins with 4 hepted repeats, follows with 18.5 EGF repeats and 31 fibronectin type III-like (FNIII) domains, and concludes with a domain homologous to fibrinogen. Several cDNA clones that have been generated by alternative splicing of eight consecutive FNIII repeats (M15-M22), as well as a proximal FNIII repeat (M3), were also identified. Less