Lv F-Z, Wang J-L, Wu Y, Chen H-F, Shen X-Y
Department of Thoracic Surgery, The Huadong Hospital, Shanghai Fudan University, Shanghai, PR China.
Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, PR China.
Int J Immunopathol Pharmacol. 2015 Mar;28(1):77-84. doi: 10.1177/0394632015572557.
Matrix metalloproteinase-12 (MMP12) is involved in many pathological processes including cancer. The expression and function of MMP12 in lung adenocarcinoma (LAC) remain unclear. The present study aimed to investigate the correlation of MMP12 expression with LAC patients and clarify its role in growth and invasion of LAC cells. The expression of MMP12 in human LAC was examined by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was used for observing the effects of lentiviral vector-mediated MMP12 shRNA (shMMP12) on cell growth and invasion in LAC cell lines (A549), indicated by MTT and Transwell assays. We found that the expression of MMP12 protein was significantly increased in LAC tissues compared with that in adjacent non-cancerous tissues (ANCT) (57.69% vs. 32.69%, P = 0.019), and was closely correlated with the pathological stage and lymph node metastasis of LAC patients (P = 0.01; P = 0.003). Knockdown of MMP12 inhibited proliferation and invasion of LAC cells followed by the downregulation of proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF). In conclusion, our findings show that high expression of MMP12 is correlated with the pathological stage and tumor metastasis of LAC patients, and knockdown of MMP12 suppresses the development of LAC cells, suggesting that MMP12 may be a promising therapeutic target for the treatment of LAC.
基质金属蛋白酶-12（MMP12）参与包括癌症在内的许多病理过程。MMP12在肺腺癌（LAC）中的表达和功能仍不清楚。本研究旨在探讨MMP12表达与LAC患者的相关性，并阐明其在LAC细胞生长和侵袭中的作用。采用组织芯片技术通过免疫组织化学分析检测人LAC中MMP12的表达。通过MTT和Transwell实验，利用功能丧失实验观察慢病毒载体介导的MMP12 shRNA（shMMP12）对LAC细胞系（A549）细胞生长和侵袭的影响。我们发现，与相邻非癌组织（ANCT）相比，LAC组织中MMP12蛋白的表达显著增加（57.69%对32.69%，P = 0.019），并且与LAC患者的病理分期和淋巴结转移密切相关（P = 0.01；P = 0.003）。敲低MMP12可抑制LAC细胞的增殖和侵袭，随后增殖细胞核抗原（PCNA）和血管内皮生长因子（VEGF）表达下调。总之，我们的研究结果表明，MMP12的高表达与LAC患者的病理分期和肿瘤转移相关，敲低MMP12可抑制LAC细胞的发展，提示MMP12可能是治疗LAC的一个有前景的治疗靶点。
