TIMP-1和TIMP-2在原发性肝癌生长、浸润及转移中的作用

Roles of TIMP-1 and TIMP-2 in the growth,invasion and metastasis of primary carcinomas of liver

目的 了解基质金属蛋白酶组织抑制因子 1(tissueinhibitorofmetalloproteinase -1,TIMP 1)和基质金属蛋白酶组织抑制因子 2 (TIMP 2 )mRNA及相关抗原在肝癌组织中的定位和表达状态 ,探讨TIMP l和TIMP 2在肝癌组织生长、浸润及转移中所起的作用。方法 以TIMP l和TIMP 2探针及单克隆抗体 (McAb)为试剂 ,采用原位杂交技术及免疫组织化学法检测原发性肝癌、肝高分化腺癌的肝组织中TIMP l和TIMP 2mRNA及相关抗原的表达 ,并与 10例正常肝组织做对照。结果 2 0例原发性肝癌患者的肝组织中TIMP l和TIMP 2mRNA及相关抗原表达的阳性率为 90 %;9例肝高分化腺癌的腺癌组织中无TIMP 1和TIMP 2mRNA及相关抗原的表达 :10例正常肝组织中TIMP l和TIMP 2mRNA及相关抗原表达均为阴性 ;TIMP l和TIMP 2mRNA及相关抗原阳性信号呈现为棕黄色颗粒状 ,分布在肝细胞浆内 ,未见细胞核着色 ;无论是原发性肝癌癌组织还是癌周组织中 ,TIMP l的表达强于TIMP 2的表达 ,癌周组织中TIMP 1和TIMP 2mRNA和相关抗原的表达与肝组织病理改变相关 ,即肝硬化者表达强 ,慢性肝炎者表达弱 ,正常肝组织无表达。结论 原发性肝癌的癌组织中存在TIMP l和TIMP 2mRNA及相关抗原的表达 ,其表达强度可能与原发性肝癌的分型有关 ,它可能通过抑制MMP的?

Aim To investigate the distribution and location of tissue inhibitor of metalloproteinase-1 and -2(TIMP-1 and TIMP-2) in carcinomas of liver and discuss the function of TIMP-1 and TIMP-2 in the growth,invasion,and metastasis of carcinomas of liver.Methods The cellular distribution of TIMP-1 and TIMP-2 was studied in surgically removed human primary carcinomas of liver and well-differentiated adenocacinoma of liver by in situ hybridization combined with immunohistochemistry using specific monoclone antibody (McAb).Results Among 20 cases with primary carcinoma of liver,TIMP-1 and TIMP-2 mRNA and protein were detected in 90% of them,and no one was found TIMP-1 or TIMP-2 mRNA positive in the 9 cases with well-differentiated adenocarcinoma and 10 normal cases.The staining signal of TIMP-1 and TIMP-2 mRNA and protein mainly located in cytoplasm of carcinomas,and no signal in the nuclear.The expression of TIMP-1 and TIMP-2 mRNA and protein with transcripts in the surrounding noncancerous cells (chronic active hepatitis or liver cirrhosis) were closely related with the extent of pathological changes of liver,and expression of TIMP-1 was stronger than that of TIMP-2 in the cancer cells and surrounding noncancarous cells.Conclusions These studies suggest that the expression intensity of TIMP-1 and TIMP-2 is probably related with the type of primary carcinoma of liver.TIMPs play an important role in HCC growth,invasion,and metastasis by inhibiting the activity of MMP and reducing the degradation of extracellular matrix.