Matrix metalloproteinase 2 contributes to aggressive phenotype, epithelial-mesenchymal transition and poor outcome in nasopharyngeal carcinoma

Background: Though matrix metalloproteinase 2 (MMP-2) involvement in tumor aggressiveness and invasion is well-known, its prognostic impacts still remain largely controversial. Furthermore, the correlations between MMP-2 and epithelial-mesenchymal transition (EMT) have not been directly established in nasopharyngeal carcinoma (NPC). Materials and methods: The purpose of this study was to investigate MMP-2 expression in NPC. Tissue microarrays from 144 patients with NPC and 45 non-cancerous pharynx tissues were analyzed for MMP-2 expression by immunohistochemistry. MMP-2 expression in relation to clinicopathological characteristics and EMT were assessed in NPC. Tumor-invasive potential affected by exogenous expression of MMP-2 in NPC cells was also detected in vitro. Results: Compared to normal nasopharyngeal epithelium, high expression of tumoral MMP-2 was detected in 47.9% of NPC samples. Significant association was found between MMP-2 expression and various aggressive features including T classification, M classification and tumor stage (P<0.05). Of note, high expression of MMP-2 was prominently observed at tumor invasive front, neoplastic spindle cells migrating into the stroma and vessel invasion. Importantly, high MMP-2 expression predicted worse survival in patients with stage III-IV (P=0.039). Overexpression of MMP-2 could decrease cell-cell adhesion, promote tumor invasion and EMT including downregulation of E-cadherin and upregulation of N-cadherin, Fibronectin and Slug of NPC cells. Conclusion: Our findings demonstrate that MMP-2 expression contributes to tumor aggressiveness and poor prognosis, and induces the occurrence of EMT in NPC.