A new anti-cancer strategy by control ling cross talk of oral carcinoma cells with extra cellular matrix molecules

为了研究抑制口腔癌细胞与细胞外基质分子的相互作用的抗癌效果的可能性，我们通过使用细胞系，例如来源于人腺样囊性癌的ACC 3或ACCM细胞，以及来源于人鳞状细胞癌的ZK-1或MK-1细胞，检查了口腔癌细胞与基质成纤维细胞之间的各种相互作用。我们检测了苏拉明（一种多磺化萘脲）对ACC 3细胞中细胞外基质（ECM）分子及其受体整联蛋白的生物合成以及它们的相互作用的影响。苏拉明增强了ACC 3细胞分泌ECM分子进入培养基，并抑制了ACC 3细胞在短期培养中的附着，这在RGD肽的存在下得到了增强。这一现象的分子机制是通过我们的实验，使用代谢标记，免疫沉淀，免疫印迹，RT-PCR，和DNA微阵列证明。苏拉明·穆塞韦尼 ...更多信息 发现黏着斑激酶（FAK）的生物合成及其通过整合素组装到细胞膜上。与此同时，FAK和其他分子的酪氨酸磷酸化被苏拉明抑制，尽管整合素和FAK的基因表达水平没有被抑制。结果表明，ACC 3细胞分泌ECM分子的增强可能是由于缺乏FAK，整合素不能被分选和组装到细胞膜上，从而不能通过整合素将ECM分子捕获在细胞表面。同时，细胞外基质分子，特别是串珠素，在各种口腔肿瘤或胚胎细胞以及基质细胞中，串珠素在口腔肿瘤细胞中也被发现在物理条件下不断降解，这可能表明串珠素被口腔肿瘤细胞代谢以促进其生长，基于本研究中获得的数据，高度表明口腔癌细胞需要与细胞外基质的串扰才能生存，并且通过抑制其对细胞外基质的识别可以抑制其增殖。少

In order to study a possibility of anti-cancer effect of inhibition of oral carcinoma cells' cross talk with extracellular matrix molecules, we examined various interactions between oral carcinoma cells and stromal fibroblasts by using cell lines, such as ACC3 or ACCM cells which were derived from human adenoid cystic carcinomas, and ZK-1 or MK-1 cells, which were derived from human squamous cell carcinomas.First of all, we examined the effect of suramin, a polysulfonated naphthylurea, on biosyntheses of extracellular matrix (ECM) molecules and their receptor integrins as well as their interaction in ACC3 cells. Suramin enhanced secretion of ECM molecules by ACC3 cells into the culture medium, and it inhibited ACC3 cells to attach in a short-term culture, that was enhanced in the presence of RGD peptides. The molecular mechanism of this phenomenon was proved by our experiments using metabolic labeling, immunoprecipitation, and immunoblotting, RT-PCR, and DNA microarrays. Suramin inhibi … More ted the biosynthesis of focal adhesion kinase (FAK) and its assembly into the cell membrane via integrins. At the same time tyrosine phosphorylation of FAK and other molecules were inhibited by suramin, although the gene expression levels for integrins and FAK were not suppressed. The results indicated that enhanced secretion of ECM molecules might result from inability of ACC3 cells to trap them on their cell surface by way of integrins, because integrins failed to be sorted and to be assembled into the cell membrane due to the absence of FAKAt the same time, the important role of extracellular matrix molecules, especially perlecan, in cellular proliferation was approved in various oral tumor or embryonal cells as well as stromal cells. Perlecan was also shown to be degraded constantly in physical conditions in oral tumor cells, which may indicate that it is metabolized by them for their growth.Based on the data obtained in this study, it is highly suggested that oral carcinoma cells require crosstalk with extracellular matrix for their survival and that their proliferation could be suppressed by the inhibition of their recognition of extracellular, matrix. Less