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目的探讨胸腺瘤和胸腺癌中基质金属蛋白酶(MMP)-2、Ⅰ型膜型(MT1)-MMP、金属蛋白酶组织抑制剂(TIMP)-2 mRNA的表达和MMP-2蛋白活性的关系。方法分别用real-tim e逆转录-聚合酶链反应(RT-PCR,Taqm an法)、明胶酶谱法和F ilm in situ gelatin-Zymography(FIZ)对正常的胸腺组织(2例)、胸腺瘤(12例)和胸腺癌(2例)患者的新鲜肿瘤组织中MMP-2、MT1-MMP、TIMP-2mRNA的表达,pro-MMP-2的活性率及活性蛋白的定位进行测定。结果MMP-2、MT1-MMP及TIMP-2 mRNA在Ⅰ期与Ⅱ期和Ⅲ期与Ⅳ期中的表达差异均无统计学意义(P>0.05),在Ⅰ~Ⅱ期与Ⅲ~Ⅳ期和胸腺癌3组中差异均有统计学意义(P<0.01)。在AB、B1型(混合型和淋巴细胞为主型)与B2、B3型(皮质型和多角细胞为主型)以及胸腺癌3组中差异均有统计学意义(P<0.05)。MMP-2的蛋白活性率(MMP-2/pro-MMP-2+MMP-2)在Ⅰ~Ⅱ期、Ⅲ~Ⅳ期和胸腺癌各组中差异有统计学意义(P<0.05),在AB、B1型与B2、B3型以及胸腺癌各组中的差异均具有统计学意义(P<0.05)。胸腺瘤各期及各型中MT1-MMP、TIMP-2 mRNA与MMP-2蛋白活性表达均呈正相关,且相关程度相似(r=0.7235、r=0.7647、P<0.005)。MMP-9的蛋白表达在各组间差异均无统计学意义。结论MMP-2、MT1-MMP及TIMP-2的mRNA表达与胸腺瘤临床分期、病理分型相关,MMP-2的活性与MT1-MMP和TIMP-2的表达升高正相关。推测MT1-MMP通过TIMP-2对MMP-2的激活起促进作用。
Objective To investigate the relationship between the expression of MMP-2, MT1-MMP and TIMP-2 mRNA and the activity of MMP-2 in thymoma and thymoma. Methods The normal thymus tissue (2 cases), thymus (25 cases) and thymus (25 cases) were treated with Real-tim e reverse transcription polymerase chain reaction (RT-PCR), gelatin zymography and F ilm in situ gelatin-Zymography The expression of MMP-2, MT1-MMP and TIMP-2 mRNA, the activity of pro-MMP-2 and the localization of active protein in fresh tumor tissue of 12 patients with breast cancer and 2 patients with thymoma were detected. Results There was no significant difference in the expressions of MMP-2, MT1-MMP and TIMP-2 mRNA between stage Ⅰ and stage Ⅱ, stage Ⅲ and stage Ⅳ (P> 0.05) Thymus cancer in the three groups differences were statistically significant (P <0.01). The difference was statistically significant (P <0.05) in AB, type B1 (predominantly mixed type and lymphocyte type) and type B2, type B3 (predominant type in cortical and polygonal cells) and in thymous carcinoma. The activity of MMP-2 / pro-MMP-2 + MMP-2 in stage Ⅰ ~ Ⅱ, stage Ⅲ ~ Ⅳ and thymoma were significantly different (P <0.05) The differences between AB, B1 and B2, B3 and thymic carcinoma groups were statistically significant (P <0.05). The expressions of MT1-MMP, TIMP-2 mRNA and MMP-2 protein in all stages and types of thymoma were positively correlated with the similarities (r = 0.7235, r = 0.7647, P <0.005). There was no significant difference in MMP-9 protein expression among the groups. Conclusion The mRNA expressions of MMP-2, MT1-MMP and TIMP-2 are correlated with the clinical stage and pathological classification of thymoma. The activity of MMP-2 is positively correlated with the increased expression of MT1-MMP and TIMP-2. It is speculated that MT1-MMP promotes the activation of MMP-2 through TIMP-2.