Overexpression of CXCR4 promotes invasion and migration of non-small cell lung cancer via EGFR and MMP-9

Abstract

The aim of the present study was to verify whether overexpression of CXC receptor 4 (CXCR4) promotes the inva- sion and migration of non-small cell lung cancer (NSCLC) via epidermal growth factor receptor (EGFR) and matrix metal- lopeptidase-9 (MMP-9), and to detect the association between CXCR4, EGFR and MMP-9. The effects of overexpression of CXCR4 on lung cancer cell functions were investigated by migration and invasion assays. Western blotting and zymo- graph assays were used to analyze the protein expression levels of EGFR and the production of MMP-9, respectively. Immunohistochemistry was applied to analyze the expression of EGFR, CXCR4 and MMP-9 in NSCLC. Statistical analyses were used to detect the associations among EGFR, CXCR4 and MMP-9 in NSCLC. Finally, survival analyses were performed. CXCR4 overexpression enhanced cell motility and invasion. CXCR4 also promoted expression of EGFR and elevated MMP-9 production. CXCR4, EGFR and MMP-9 were highly expressed in NSCLC, and were not identified as associated with age and sex (P>0.05). However, they were associated with tumor differentiation and lymph node metas- tasis (P<0.05). CXCR4, EGFR and CXCR4 expression were positively associated with one another in NSCLC (P<0.05). In addition, patients with positive expression of CXCR4, EGFR or MMP-9 in tumors exhibited significantly shorter overall survival compared with those with negative expression (P<0.05). In conclusion, CXCR4 overexpression enhanced cell motility and invasion via EGFR and MMP-9. CXCR4, EGFR and MMP-9 were identified as highly expressed in NSCLC, and there was positive correlation among them.