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

控制口腔癌细胞与细胞外基质分子串扰的新抗癌策略

基本信息

批准号：
13557157
负责人：
SAKU Takashi
金额：
$ 9.02万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

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

为了研究口服癌细胞与临时基质分子的抗癌作用，通过使用人类腺样细胞系统和ZK-1或MK-1细胞的细胞系在口腔癌细胞和基质Firoblasts之间的各种相互作用，这些相互作用是源自人类的s骨。在所有苏拉米蛋白（一种苏拉蛋白）（一种多硫化萘）上，在外胞外基质（ECM）分子（ECM）分子的生物合成上及其受体整合蛋白作为ACC3细胞中的ECM分子的相互作用。在RGD肽的存在下，培养物得到了增强。激酶（FAK）通过整联蛋白在同一酪氨酸的磷酸化中被抑制在同一酪氨酸磷酸化中。它们的细胞表面通过整合的方式，由于缺乏FAKAT，整联蛋白未能组装到细胞膜中。或胚胎细胞作为基质细胞。矩阵的生存和priliferd可以通过抑制其对细胞外的基质的抑制。