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

Zuo,Jianhong; Wen,Meiling; Li,Sai; Lv,Xiu; Wang,Lei; Ai,Xiaohong; Lei,Mingsheng

doi:10.3892/ol.2017.7168

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

Authors:
- Jianhong Zuo
- Meiling Wen
- Sai Li
- Xiu Lv
- Lei Wang
- Xiaohong Ai
- Mingsheng Lei
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Affiliations: Hunan Province Key Laboratory of Tumor Cellular and Molecular Pathology, Cancer Research Institute, School of Medicine, University of South China, Hengyang, P.R. China, Department of Radiotherapy, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China, Department of Respiratory, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
Published online on: October 11, 2017 https://doi.org/10.3892/ol.2017.7168
Pages: 7513-7521

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Abstract

The aim of the present study was to verify whether overexpression of CXC receptor 4 (CXCR4) promotes the invasion and migration of non‑small cell lung cancer (NSCLC) via epidermal growth factor receptor (EGFR) and matrix metallopeptidase‑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 zymograph 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 metastasis (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.

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