Correlation between MMP-2 activation and MT1-MMP mRNA expression in thymic epithelial tumors

Abstract

To study the relationship between activation of pro-MMP-2 and expression of matrix metalloproteinases (MMP)-2, MT1-MMP and tissue inhibitor of metalloproteinases (TIMP)-2 mRNA in thymoma and thymic carcinoma; and to study the molecular mechanism of invasion and metastasis of thymic epithelial tumors. Fresh tissue specimens of thymoma, thymic carcinoma and normal thymus were included. The mRNA expression of MMP-2, MT1-MMP and TIMP-2 were analyzed by real-time reverse transcription polymerase chain reaction. The pro-MMP-2 activation ratio and its localization were determined by gelatin zymography and film in-situ gelatin-Zymography, respectively. Correlation of mRNA expression of MMP-2, MT1-MMP and TIMP-2 was investigated in tumors with different histological subtypes and clinical stages. There were no significant differences in the expressions of MMP-2, MT1-MMP and TIMP-2 mRNA between I and II stage or III and IV stage thymomas (P > 0.05). However, significant differences of the expressions were observed between three tumor groups: I-II stage, III-IV stage and thymic carcinomas (P < 0.005), and between three histological subtypes: AB-B1 (lymphocyte-rich and mixed types), B2-B3 (cortical and predominantly polygonal cells types) and thymic carcinomas (P < 0.05). Expression levels of MT1-MMP and TIMP-2 mRNA were correlated with pro-MMP-2 activation ratio (Spearman rank correlation: r = 0.7235, r = 0.7647, P < 0.005). The expression of MMP-9 did not show significant differences between thymomas and thymic carcinomas. MMP-2, MT1-MMP and TIMP-2 mRNA expression levels are correlated with the histologic subtypes and clinical stages of thymoma. The mRNA expressions of MT1-MMP and TIMP-2 are correlated with the activation ratio of pro-MMP-2. It is speculated that upregulation of MT1-MMP gene expression may induce an activation of pro-MMP-2 through TIMP-2.