Shrestha P, Sumitomo S, Lee C H, Nagahara K, Kamegai A, Yamanaka T, Takeuchi H, Kusakabe M, Mori M
Department of Oral and Maxillofacial Surgery, Asahi University School of Dentistry, Tsukuba City, Japan.
Eur J Cancer B Oral Oncol. 1996 Mar;32B(2):106-13. doi: 10.1016/0964-1955(95)00074-7.
Tenascin (TN), a recently characterised extracellular matrix protein, largely confined to the process with the development of embryo in areas 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 variety 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 gland adenocarcinoma cells (SGT-1), normal mouse embryonic fibroblasts (NIH3T3-3) and K-ras-2 transformed fibroblasts (Cle-H3) in an in vitro study 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 itself was found to possess a growth-enhancing activity. Moreover, studies 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 affected the cellular adhesion and morphology. In SCCKN and SGT-1, but not in NIH3T3 and Cle-He3 fibroblasts, a higher concentration of TN inhibited cellular adhesion on fibronectin, suggesting that cells attach poorly on TN, it may interfere with the action of fibronectin, and the 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 lost their cell to cell contact and were seen to be separating. The presence of these extracellular matrix proteins were further tested to determine whether they could modulate the secretion of proteolytic enzymes responsible for extracellular matrix degradation by tumour cells, when the neoplastic cells but not the non-neoplastic cells grown on FN/TN substrate showed positive immunofluorescence for collagenase. FN, LN or TN alone did not induce collagenase in the tumour cells. If the same is true in vivo, although a number of factors and interactions may implicate the ultimate outcome, the enhanced expression of TN in neoplastic lesions may have potential implications for tumour growth, differentiation, cellular adhesion, invasion and metastasis.
腱生蛋白（TN）是一种最近被鉴定的细胞外基质蛋白，在胚胎发育过程中主要局限于上皮-间充质相互作用区域以及存在形态发生运动和组织模式形成的区域，在成体组织中的表达高度受限。TN在多种人类肿瘤性病变中表达增强。然而，其在肿瘤性病变中表达增强的功能及分子机制仍不清楚。我们在一项体外研究中使用了人舌癌细胞（SCCKN）、人涎腺腺癌细胞（SGT-1）、正常小鼠胚胎成纤维细胞（NIH3T3-3）和K-ras-2转化的成纤维细胞（Cle-H3）来阐明TN的生物学作用。在体外研究中，所有检测的细胞系在转化生长因子-β存在的情况下均以剂量依赖方式增强了TN的分泌，并且发现TN本身具有生长促进活性。此外，对细胞系在纤连蛋白（FN）、层粘连蛋白（LN）、腱生蛋白（TN）、TN/FN和TN/LN包被底物上的黏附研究表明，所有细胞在FN和LN上均能良好地黏附并铺展。然而，在TN上它们黏附较差且保持圆形。TN和FN的相对浓度影响细胞黏附和形态。在SCCKN和SGT-1中，但在NIH3T3和Cle-He3成纤维细胞中未观察到，较高浓度的TN抑制细胞在纤连蛋白上的黏附，这表明细胞在TN上黏附较差，它可能干扰纤连蛋白的作用，并且TN、FN或LN的相对浓度可能影响细胞黏附和形态，这在不同细胞类型中可能有所不同。当将TN添加到指数生长细胞的生长培养基中时，细胞失去细胞间接触并被观察到正在分离。进一步检测这些细胞外基质蛋白的存在，以确定它们是否可以调节负责肿瘤细胞降解细胞外基质的蛋白水解酶的分泌，但在FN/TN底物上生长的肿瘤细胞而非非肿瘤细胞对胶原酶呈阳性免疫荧光。单独的FN、LN或TN不会在肿瘤细胞中诱导胶原酶。如果在体内也是如此，尽管许多因素和相互作用可能与最终结果有关，但TN在肿瘤性病变中表达增强可能对肿瘤生长、分化、细胞黏附、侵袭和转移具有潜在影响。
