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

应用微阵列分析技术，结合肿瘤相关DNA芯片技术，对有转移潜能（MK-1和ACCM）和无转移潜能（ZK-1/ZK-2和ACC 2/ACC 3）的人口腔/唾液腺癌细胞系的基因表达差异进行分析，以确定哪些基因与肿瘤转移行为相关。ACC 2/ACC 3和ACCM之间或ZK-1/ZK-2和MK-1之间通常共享负责细胞生长、凋亡、细胞骨架、细胞外基质分子代谢和细胞附着的基因的mRNA表达水平的显著差异。具有高转移潜能的ACCM和/或MK-1在细胞外基质相关分子如IV/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、血小板反应蛋白1/2和CD 44抗原中显示较低水平的基因表达，但在控制细胞外基质降解如MMP 9/15以及细胞生长和细胞周期的基因中显示较高水平的基因表达，如FGF 3、FGF 7、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和腺嘌呤磷酸核糖基转移酶。通过免疫荧光证实ACCM中FGF 7的较高蛋白表达水平和IV型胶原和层粘连蛋白的较低蛋白水平。口腔/唾液腺癌细胞的转移潜力似乎是由某些基因的过度/低表达的组合引起的，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.