A variety of molecular crosstalks between extracellular matrices and their cell surface receptors in oral carcinomas

我们分析了口腔癌细胞的细胞外基质（ECM）分子的生物合成，如从人腺样囊性癌细胞中建立的ACC3，从口腔鳞状细胞癌中建立的MK-1和ZK-1。这些癌细胞显示产生基底膜相关分子，特别是基底膜型硫酸肝素蛋白多糖，HSPG/perlecan和纤维连接蛋白FN。这两种ECM分子的分子量随细胞类型的不同而不同。我们研究了分子大小变化的分子背景，通过免疫沉淀的35s -蛋氨酸标记细胞与几种低聚糖裂解酶的组合。ACC3细胞产生了高分子量的HSPG/FN，这是由于HSPG核心蛋白的选择性剪接和n -和o -连接的低聚糖链的加入导致了更大的蛋白，尽管对HSPG核心蛋白的选择性剪接机制还需要更多的研究。同样，这些细胞表达的整合素、INTs、受体……更多的是ECM分子，它们的大小不同。这主要是由于低聚糖的添加。因此，在口腔癌细胞中，ECM分子及其受体存在多种结构。由于ECM分子大小与细胞的附着能力平行，提示ECM分子大小调节了癌细胞的生物学性质，而ECM分子大小随癌细胞类型的变化而变化。ECM分子与其受体之间的这种多种分子串扰也应反映在口腔癌的组织结构以及肉芽组织的组织重塑过程中。我们也将这些分子免疫定位于口腔肿瘤和炎症病变。针对这些免疫组织化学实验，我们提出了各种组织类型中ECM分子的酶预处理指南。这些结果清楚地表明，ECM分子及其受体的分子结构随细胞类型而变化，这种分子多样性应反映在其临床过程中。然而，目前的研究尚不清楚是什么调节了这些分子的多样性，以及这些多样性是否在体外的人类癌组织中实际起作用。少

We have analyzed biosynthesis of extracellular matrix(ECM)molecules by oral carcinoma cells, such as ACC3 established from a human adenoid cystic carcinoma cells, MK-1 and ZK-1 established from oral squamous cell carcinomas. These carcinoma cells were shown to produce basement membrane-associated molecules, especially basement membrane type heparan sulfate proteoglycan, HSPG/perlecan, and fibronectin, FN.These two ECM molecules were different in molecular weight with cell types. We examined the molecular background for the variations in molecular size among them, by using immunoprecipitation of 35S-methionin labeled cells with several combinations of oligosaccharide lyases. ACC3 cells produced high molecular weight HSPG/FN, which were resulted from larger proteins due to alternative splicing and addition of N-and O-linked oligosaccharide chains, although more investigations are necessary for the alternative splicing mechanism for HSPG core protein.Similarly, integrins, INTs, receptors … More for ECM molecules, expressed by these cells were different in size. This was mainly due to oligosaccharide additions. Thus, there was a variety of structures of ECM molecules and their receptors among oral carcinoma cells. Since the molecular sizes were parallel with the attachment ability of the cells, it is suggested that the ECM molecular size, which is varied with carcinoma cell types, regulate the biological nature of them.Such a variety of molecular crosstalks between ECM molecules and their receptors should be also reflected to the tissue architecture of oral carcinomas as well as tissue remodeling processes of granulation tissues. We also immunolocalized these molecules in oral neoplastic and inflammatory lesions. In relation to these immunohistochemical experiments, we proposed a guideline for enzymatic pretreatments for ECM molecules in various tissue types.These results clearly indicate that the molecular structures of ECM molecules and their receptors vary with cell types and that the molecular variety should be reflected in their clinical courses. However, it is unknown from the present study what regulates such molecular variety and if these varieties are actually functions in human carcinoma tissues in vitro. Less