Ramos D M, Chen B L, Boylen K, Stern M, Kramer R H, Sheppard D, Nishimura S L, Greenspan D, Zardi L, Pytela R
Department of Stomatology, UCSF, San Francisco, CA 94143-0512, USA.
Int J Cancer. 1997 Jul 17;72(2):369-76. doi: 10.1002/(sici)1097-0215(19970717)72:2<369::aid-ijc28>3.0.co;2-9.
In this study we identified tenascin-C (TN-C) and one of its integrin receptors, alpha(v)beta6, in oral squamous-cell carcinoma (SCC) specimens. Neither TN-C nor alpha(v)beta6 are expressed in normal oral mucosa. We also studied 2 human oral squamous-cell carcinoma cell lines: the highly invasive HSC-3 cells, and the poorly invasive SCC-25 cells. We determined that adhesion of these cells to TN-C involves both alpha2 and alpha(v) integrins. Migration on TN-C by oral SCC cells required fibroblast-conditioned medium and did not occur in its absence. This migration was blocked by anti-alpha2 and anti-alpha(v) antibodies and was partially inhibited by antibodies to hepatocyte growth factor, epidermal growth factor and transforming growth factor-beta1. When seeded on TN-C, the poorly invasive SCC-25 cells formed alpha(v)beta6-positive focal contacts; the HSC-3 cells did not. HSC-3, SCC-25 and PTF cells secrete TN-C into the culture medium, as determined by Western blot. However, when HSC-3 cells were inoculated into the floor of the mouth of nude mice, only murine TN-C could be identified in the reactive stroma adjacent to the resulting tumor nests, demonstrating that in vivo, HSC-3 cells do not secrete TN-C. Our results demonstrate that alpha(v)beta6 and tenascin-C are neo-expressed in oral squamous-cell carcinoma, and that the tumor stromal environment is influential in oral SCC behavior.
在本研究中，我们在口腔鳞状细胞癌（SCC）标本中鉴定出了肌腱蛋白-C（TN-C）及其整合素受体之一α(v)β6。TN-C和α(v)β6在正常口腔黏膜中均不表达。我们还研究了2种人类口腔鳞状细胞癌细胞系：高侵袭性的HSC-3细胞和低侵袭性的SCC-25细胞。我们确定这些细胞与TN-C的黏附涉及α2和α(v)整合素。口腔SCC细胞在TN-C上的迁移需要成纤维细胞条件培养基，在没有该培养基的情况下则不会发生迁移。这种迁移被抗α2和抗α(v)抗体阻断，并被针对肝细胞生长因子、表皮生长因子和转化生长因子-β1的抗体部分抑制。当接种在TN-C上时，低侵袭性的SCC-25细胞形成α(v)β6阳性的黏着斑；HSC-3细胞则没有。通过蛋白质印迹法测定，HSC-3、SCC-25和PTF细胞将TN-C分泌到培养基中。然而，当将HSC-3细胞接种到裸鼠的口腔底部时，在与形成的肿瘤巢相邻的反应性基质中只能鉴定出鼠源TN-C，这表明在体内，HSC-3细胞不分泌TN-C。我们的结果表明，α(v)β6和肌腱蛋白-C在口腔鳞状细胞癌中重新表达，并且肿瘤基质环境对口腔SCC的行为有影响。
