TENASCIN - GROWTH AND ADHESION MODULATION EXTRACELLULAR-MATRIX DEGRADING FUNCTION - AN IN-VITRO STUDY

Tenascin (TN), a recently characterised extracellular matrix protein, largely confined to the process with the development of embryo in area s of epithelial-mesenchymal interactions and in areas where there are morphogenetic movements and tissue patterning, has a highly restricted expression in adult tissues. The expression of TN is enhanced in a va riety of human neoplastic lesions. However, function(s) and molecular mechanisms of enhanced expression in neoplastic lesions remain unclear . We employed human tongue carcinoma cells (SCCKN), human salivary gla nd adenocarcinoma cells (SGT-1), normal mouse embryonic fibroblasts (N IH3T3-3) and K-ras-2 transformed fibroblasts (Cle-H3) in an in vitro s tudy to elucidate the biological roles of TN. In in vitro studies, all the cell lines examined had enhanced secretion of TN in the presence of transforming growth factor-beta in a dose-dependent manner and TN i tself was found to possess a growth-enhancing activity. Moreover, stud ies on adhesion of the cell lines on coated substrates of fibronectin (FN), laminin (LN), tenascin (TN), TN/FN and TN/LN showed that all the cells adhere and spread well on FN and LN. However, on TN they attach poorly and remain rounded. The relative concentrations of TN and FN a ffected the cellular adhesion and morphology. In SCCKN and SGT-1, but not in NIH3T3 and Cle-He3 fibroblasts, a higher concentration of TN in hibited cellular adhesion on fibronectin, suggesting that cells attach poorly on TN, it may interfere with the action of fibronectin, and th e relative concentrations of TN, FN or LN may affect cellular adhesion and morphology which may differ in different cell types. When TN was added in the growth medium of exponentially growing cells, the cells l ost their cell to cell contact and were seen to be separating. The pre sence of these extracellular matrix proteins were further tested to de termine whether they could modulate the secretion of proteolytic enzym es responsible for extracellular matrix degradation by tumour cells, w hen the neoplastic cells but not the non-neoplastic cells grown on FN/ TN substrate showed positive immunofluorescence for collagenase. FN, L N or TN alone did not induce collagenase in the tumour cells. If the s ame is true in vivo, although a number of factors and interactions may implicate the ultimate outcome, the enhanced expression of TN in neop lastic lesions may have potential implications for tumour growth, diff erentiation, cellular adhesion, invasion and metastasis. (C) 1996 Else vier Science Ltd