基质金属蛋白酶-2,-9及其抑制剂1在肺癌侵袭转移中的作用

Study on the roles of matrix metalloproteinases-2,-9 and tissue inhibitor of metalloproteinaes-1 in lung cancer invasion and metastasis

目的 探讨基质金属蛋白酶 2 (MMP 2 )、MMP 9及基质金属蛋白酶组织抑制剂1(TIMP 1)在肺癌侵袭转移机制中的作用。方法 收集30例经病理证实的肺癌患者和15例健康志愿者,将肺癌患者分为两组:无远处转移组(Ⅱ～Ⅲ期) 15例,远处转移组(Ⅳ期) 15例,分别用逆转录聚合酶链(RT PCR)方法测定各组患者静脉血白细胞中MMP 9、TIMP 1mRNA的表达;用聚丙烯酰胺明胶电泳法测定各组患者血浆中MMP 2、MMP 9含量,分析其与肺癌分期的关系,以及白细胞中MMP 9的mRNA表达与血浆中MMP 9蛋白水平的相关性。结果 肺癌患者外周血白细胞中MMP 9的mRNA表达和MMP 9/TIMP 1比值与正常对照组相比均显著升高(P <0 0 0 0 1) ;Ⅳ期肺癌患者比Ⅱ～Ⅲ期明显升高(P <0 0 0 0 1)。肺癌患者外周血白细胞中TIMP 1的mRNA表达与正常对照组相比无明显差异(P >0 0 5 )。肺癌患者各组血浆中MMP 9蛋白水平与正常对照组比较均升高(P <0 0 0 0 1) ;Ⅳ期肺癌患者比Ⅱ～Ⅲ期明显升高(P <0 0 0 5 )。肺癌患者各组血浆中MMP 2蛋白水平表达与正常对照组相比无明显差异(P >0 0 5 )。外周血白细胞中MMP 9mRNA表达与血浆中MMP 9蛋白水平呈正相关(r=0 4 15 ,P <0 0 5 )。结论 MMP 9/TIMP

Objective To evaluate the roles of matrix metalloproteinases-2 (MMP-2),MMP-9 and its inhibitor tissue inhibitor of metalloproteinases-1 (TIMP-1) in the invasion and metastasis of lung cancer.Methods 30 patients with lung cancer from stage Ⅱ to stage Ⅳ and 15 normal subjects were enrolled.The mRNA express of MMP-9 and TIMP-1 in white blood cells was measured by RT-PCR quantitative analysis.The MMP-2 and MMP-9 levels in the plasma were assayed by Gelatin Zymography.The relationships between MMP-2, MMP-9,TIMP-1 and the disease stages were analyzed.Results MMP-9 mRNA expression and the ratio of MMP-9 to TIMP-1 were higher in patients with lung cancer (P<0.000 1) than those in control group.There were significant differences of MMP-9 mRNA expression and the ratio of MMP-9 to TIMP-1 between the subjects of stageⅡ～Ⅲ and those of stage Ⅳ (P< 0.000 1),but no differences of TIMP-1 mRNA expression was found (P>0.05).MMP-9 levels in plasma were higher in lung cancer groups than those in control group (P< 0.000 1)and elevated progressively with advance of the disease.No significant differences in MMP-2 levels were found between the subjects with lung cancer and normal controls (P>0.05).There was positive correlation between MMP-9 mRNA expression in white blood cells and the MMP-9 levels in plasma (r=0.415).Conclusion The imbalanced between MMP-9 and TIMP-1 may play a role in lung cancer invasion and metastasis.