基质金属蛋白酶的表达与肝癌侵袭转移的关系

目的　揭示基质金属蛋白酶 -2 (MMP -2 )、基质金属蛋白酶 -9(MMP -9)在肝细胞癌的表达及其与侵袭转移过程中的表达关系 ,进一步了解肝细胞癌侵袭转移的发生机制。方法　通过免疫组化SABC法 ,检测 3 2只大鼠的肝细胞癌模型标本肝癌及癌旁肝组织MMP -2及MMP -9的表达 ,应用图像分析法进行定量分析MMP -2及MM -9的变化。门静脉癌栓形成作为肝细胞癌侵袭转移标志。结果　免疫组化显示 ,癌及其癌旁肝组织均有MMP -2及MMP -9表达 ,MMP -2及MMP -9在肝癌组织的表达显著高于癌旁肝组织 (P <0 0 1) ;MMP -2及MMP -9在有侵袭转移肝癌组织的表达显著高于无侵袭转移肝癌组织 (P <0 0 1)。MMP -2及MMP -9在无侵袭转移肝癌、癌旁肝组织及有侵袭转移癌旁肝组织的表达差异无显著性 (P >0 0 5 ) ;肝癌组织中MMP -2及MMP -9含量高于相对应癌旁肝组织时 ,发生癌栓的机会至少为 42 9% ,当癌组织中MMP -2及MMP -9含量低于癌旁肝组织时癌栓发生率为 0。结论　肝细胞癌在有侵袭转移情况下MMP -2及MMP -9在癌组织表达明显增高。预示可通过检测癌组织MMP -2及MMP -9表达水平帮助判断肝癌复发、转移风险。因此 ,提示其极有可能成为防治肝细胞癌的生物学标志物

Relationship between the expression of matrix metalloproteinases and invasion and metastasis of hepatocellular cancer

Objective To investigate the dynamic alteration of the latent and activated forms of MMP-2 and MMP-9 in rat liver tissue during experimental hepatocarcinoma and the effects of matrix metalloproteinase on the growth and invasion and metastasis of hepatocellular carcinoma and its mechanisms. Methods Immunohistochemistry was used for defection of MMP-2 and MMP-9 protein during the developmen of diethylnitrosamine-induced rat hepatocacinoma. The expression of MMP-2 and MMP-9 was analyzed with image analyzing. Tumor cells emboli in porta vein were marker for matastasis of hepatocellular carcinoma.Results MMP-2 and MMP-9 were expressed in carcinoma and tissue close to tumor, and the former expressed higher than the later( P <0 01); Content of MMP-2 and MMP-9 in tumors was higher if hapatocellular carcinoma matastasised or transferred. In our groups, MMP-2 and MMP-9 expression in matastasised tissues was significantly higher than that in non-matastasised tissues( P <0 01). No difference in expression of MMP-2 and MMP-9 was showed in non-transferred tumors, normal tissues close to tumor and tissues close to transferred tumors( P >0 05). The probability of tumor emboli was at least 42 9% when the content of MMP-2 and MMP-9 in tumor cells were higher than those in tissues close to tumor cells, and the probability was zero when the content of MMP-2 and MMP-9 was lower than that of tissue close to tumor cells.Conclusion We may diagnose relapsed or transferred tumors through detecting the level of MMP-2 and MMP-9 in tumor tissues and inhibit tumor grow through decreasing the expression of MMP-2 and MMP-9 by matrix matalloproteinases. MMP-2 and MMP-9 are likely to be biological markers for prevention and treatment of hepatocellular carcinoma.