Metastasis-associated genes in salivary adenoid cystic carcinoma and oral squamous cell carcinoma : a differential DNA chip analysis between metastatic and non-metastatic cell systems

通过肿瘤相关DNA芯片的微阵列分析，分析具有（MK-1和ACCM）和不具有（ZK-1/ZK-2和ACC2/ACC3）转移潜能的人口腔/唾液癌细胞系统差异基因表达的总体模式，以确定哪些基因与转移行为相关。在ACC2/ACC3和ACCM之间或ZK-1/ZK-2和MK-1之间，负责细胞生长、凋亡、细胞骨架、细胞外基质分子代谢和细胞附着的基因mRNA表达水平存在显著差异。ACCM和/或MK-1具有高度转移潜力，细胞外基质相关分子如IV型/XVII型胶原和层粘连蛋白，粘附分子如整合素α 2/3、钙粘蛋白2、血栓反应蛋白1/2和CD44抗原的基因表达水平较低，而控制细胞外基质降解的基因如MMP 9/15，细胞生长和细胞周期的基因如FGF3、FGF7、干燥综合征/硬皮病自身抗原1、细胞周期蛋白依赖性激酶4和细胞周期蛋白D1与腺嘌呤磷酸核糖基转移酶。免疫荧光显示，FGF7在ACCM中表达水平较高，而IV型胶原和层粘连蛋白表达水平较低。口腔/唾液癌细胞的转移潜力似乎是由一些基因的过表达/过表达的组合引起的，这些基因特别负责细胞生长和细胞外基质代谢。

Overall modes of differential gene expressions were analyzed between human oral/salivary carcinoma cell systems with(MK-1 and ACCM) and without(ZK-1/ZK-2 and ACC2/ACC3) metastatic potential by using micro-array analysis with cancer-associated DNA chips, to determine what kinds of genes were associated with metastatic behaviors. Conspicuous differences in the level of mRNA expression of genes, which are responsible for, cell growth, apoptosis, cytoskeletons, extracellular matrix molecules metabolism, and cellular attachment were commonly shared between ACC2/ACC3 and ACCM or between ZK-1/ZK-2 and MK-1. ACCM and/or MK-1,which have highly metastatic potential, showed lower levels of gene expression in extracellular matrix-related molecules, such as collagens type IV/XVII and laminin, such adhesion molecules as integrins alpha 2/3, cadherin 2,thrombospondin 1/2 and CD44 antigen, but higher levels of genes controlling extracellular matrix degradation, such as MMP 9/15, and cell growth and cell cycle, such as FGF3,FGF7,Sjogren's syndrome/scleroderma autoantigen 1, cyclin dependent kinase 4 and cyclin D1 and adenine phosphoribosyltransferase. The higher protein expression levels for FGF7 in ACCM and lower protein levels for Collagen type IV and laminin were conformed by immunofluorescence. Metastatic potentials of oral/salivary carcinoma cells seem to be resulted from some combinations of over-/under-expression of the genes, which are responsible particularly for cell growth and extracellular matrix metabolism.