Zuo Jianhong, Wen Meiling, Li Sai, Lv Xiu, Wang Lei, Ai Xiaohong, Lei Mingsheng
Hunan Province Key Laboratory of Tumor Cellular and Molecular Pathology, Cancer Research Institute, School of Medicine, University of South China, Hengyang, Hunan 421001, P.R. China.
Department of Radiotherapy, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
Oncol Lett. 2017 Dec;14(6):7513-7521. doi: 10.3892/ol.2017.7168. Epub 2017 Oct 11.
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.
本研究的目的是验证CXC趋化因子受体4（CXCR4）的过表达是否通过表皮生长因子受体（EGFR）和基质金属蛋白酶-9（MMP-9）促进非小细胞肺癌（NSCLC）的侵袭和迁移，并检测CXCR4、EGFR和MMP-9之间的关联。通过迁移和侵袭实验研究CXCR4过表达对肺癌细胞功能的影响。分别采用蛋白质免疫印迹法和酶谱分析法分析EGFR的蛋白表达水平和MMP-9的产生情况。应用免疫组织化学法分析NSCLC中EGFR、CXCR4和MMP-9的表达。采用统计学分析检测NSCLC中EGFR、CXCR4和MMP-9之间的关联。最后进行生存分析。CXCR4过表达增强了细胞的运动性和侵袭能力。CXCR4还促进了EGFR的表达并提高了MMP-9的产生。CXCR4、EGFR和MMP-9在NSCLC中高表达，且与年龄和性别无关（P>0.05）。然而，它们与肿瘤分化和淋巴结转移有关（P<0.05）。在NSCLC中，CXCR4、EGFR和CXCR4的表达彼此呈正相关（P<0.05）。此外，肿瘤中CXCR4、EGFR或MMP-9表达阳性的患者与表达阴性的患者相比，总生存期显著缩短（P<0.05）。总之，CXCR4过表达通过EGFR和MMP-9增强了细胞的运动性和侵袭能力。CXCR4、EGFR和MMP-9在NSCLC中高表达，且它们之间存在正相关。
