PILOT--TENASCIN AND ITS RECEPTOR IN ORAL CANCER

肿瘤的侵袭和转移是一个复杂的过程，涉及多个 肿瘤细胞与多种细胞外基质的相互作用 蛋白质。许多基质成分，如层粘连蛋白和纤维连接蛋白，具有 对它们在肿瘤中的可能作用进行了详细的研究 进步。然而，很明显，其他细胞-基质相互作用 也在这一过程中发挥作用。在这个项目中，它被提议 研究Tn及其受体α-v-Tn的表达。 在口腔鳞状细胞癌的进展过程中，TN是一种 一种大的寡聚糖蛋白，它暂时存在于 发育过程中的细胞外基质，并参与形态发生 运动、组织构图和组织修复。Tenascin有多个 与细胞相互作用的结构域，包括粘性和抗粘性， 纤维连接蛋白和其他细胞外基质蛋白。有几个 由选择性剪接产生的分子的异构体。这个 TN选择性剪接区的生物学意义 几份报告强调了这一点，报告显示，大的TN剪接 Variant是在重要的细胞过程开始时表达的 需要主动的细胞迁移或组织重塑。最近，它一直在 研究表明Tenascin在口腔癌中表达上调(Tiita et 等人，1994年)。Tenascin的受体Alpha-v-beta-6也已被 在口腔鳞状细胞癌中表达上调，尽管没有 在正常口腔粘膜中表达(Breuss et al.，1995)。所以就像Tenascin一样， α-v-β-6在正常组织中不存在，但在 在肿瘤情况下的显著水平。 这项研究的假设是Tenascin在 口腔癌直接作为刺激调节因子的进展 肿瘤细胞的运动性、侵袭性或基因表达 与整合素α-v-β-6的相互作用。这样做的具体目的是 建议如下：(1)评估Tenascin和Tenascin的表达 其选择性剪接异构体和口腔癌中的α-v-β-6， (2)用β-6和β-6建立口腔癌动物模型 Tenascin“敲除”小鼠。这些研究应该会丰富我们的理解 Tenascin等新型基质蛋白及其受体的表达 受体α-v-β-6参与口腔癌的进展。

Tumor invasion and metastasis is a complex process involving multiple interactions between tumor cells and a variety of extracellular matrix proteins. Many matrix components, such as laminin and fibronectin, have been studied in detail regarding their putative roles in tumor progression. However, it is apparent that other cell-matrix interactions also play a role in this process. In this project it is proposed to investigate the expression of tenascin (-TN) and its receptor, alpha-v- beta-6, during the progression of oral squamous cell carcinoma TN is a large oligomeric glycoprotein which is present transiently in the extracellular matrix during development and is involved in morphogenic movements, tissue patterning and tissue repair. Tenascin has multiple domains, both adhesive and anti-adhesive, that interact with cells, fibronectin, and other extracellular matrix proteins. There are several isoforms of the molecule which result from alternative splicing. The biological significance of the alternatively spliced region of TN has been emphasized by several reports showing that the large TN splice variant is expressed at the onset of important cellular processes that need active cell migration or tissue remodeling. Recently, it has been shown that tenascin expression is upregulated in oral cancer (Tiita et al., 1994). Alpha -v-beta-6, a receptor for tenascin, has also been shown to be upregulated, in oral squamous cell carcinoma, although not expressed in normal oral mucosa (Breuss et al., 1995). So like tenascin, alpha-v-beta-6 is absent from normal tissue but is expressed at significant levels in the neoplastic condition. The hypothesis of this study is that tenascin plays a role in the progression of oral cancer by acting directly as a stimulatory modulator of tumor cell motility, invasion, or gene expression through interactions with the integrin alpha-v-beta-6. The specific aims of this proposal are as follows: (1) To evaluate the expression of tenascin and its alternatively spliced isoforms and alpha-v-beta-6 in oral cancer, (2) To establish an animal model of oral carcinogenesis using beta-6 and tenascin "knockout" mice. These studies should enrich our understanding of how the expression of novel matrix proteins like tenascin and its receptor, alpha-v-beta-6, participates in oral cancer progression.