MT2-MMP expression associates with tumor progression and angiogenesis in human lung cancer.

Matrix metalloproteinases (MMPs) are a family of important proteolytic enzymes that play an important role in the remodeling of the tumor microenvironment and associate with tumorigenesis and metastasis. We previously reported that membrane type-2 MMP (MT2-MMP) is highly expressed in human esophageal cancer tissues, and its expression level is positively correlated to tumor size and intratumoral angiogenesis. In order to reveal whether MT2-MMP expression is operative in human lung cancer and its underlying physio-pathological role, in the present study, we examined both mRNA and protein expression levels of MT2-MMP in non-small cell lung caner (NSCLC) tissues and in adjacent normal tissues by using real-time RT-PCR and immunohistochemistry respectively, which showed that both MT2-MMP mRNA (P=0.0359) and protein (P<0.0001) expression levels were significantly increased in cancer tissues in contrast to adjacent normal tissues. Moreover, we also found that the MT2-MMP protein level in cancer tissues positively correlated to lymph node metastasis (P=0.0483), tumor stage (P=0.0483), intra-tumoral microvessel density (MVD) (P=0.0445). We have not found statistically significant correlation between MT2-MMP expression and patients' prognoses, but we found that the patients with both higher MT2-MMP protein expression and higher intra-tumoral microvessel density showed better prognoses than that of the patients with either higher MT2-MMP protein expression or higher intra-tumoral microvessel density (P=0.0311). Thus, our data suggest that MT2-MMP expression positively involves in NSCLC, and might play an important role in promoting the tumor progression and intra-tumoral angiogenesis in NSCLC.