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

点击翻译按钮获取中文摘要

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