Matrix metalloproteinase 2 promotes cell growth and invasion in colorectal cancer

• Published in: Acta biochimica et biophysica Sinica 2011-11, Vol.43 (11), p.840-848
• Main Authors: Dong, Wei, Li, Hong, Zhang, Yan, Yang, Heng, Guo, Min, Li, Li, Liu, Tongjun
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - enzymology; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; Cell Growth Processes; Cell Line, Tumor; Cell Movement; Colorectal Neoplasms - enzymology; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Female; Follow-Up Studies; HT29 Cells; Humans; Male; Matrix Metalloproteinase 14 - metabolism; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 2 - metabolism; Middle Aged; Multivariate Analysis; Neoplasm Invasiveness; Survival Analysis; Vascular Endothelial Growth Factor A - metabolism; VEGF; 侵袭; 基质金属蛋白酶; 大肠癌; 细胞生长; 肿瘤浸润; 蛋白质水平; 血管内皮生长因子
• ISSN: 1672-9145; 1745-7270
• DOI: 10.1093/abbs/gmr085

Colorectal cancer （CRC） is the third leading cause of cancer-related death in the western world. In this study, we evaluated the expression of matrix metalloproteinase 2 gene （MMP2） in CRC and analyzed its correlation with clinicopathological features. We found that the expression of MMP2 was significantly higher in CRC tissues than in the colorectai tissues. In addition, high levels of MMP2 protein were positively correlated with the status of tumor size, lymph node metastasis, distant metastasis, Dukes＇ stage, and tumor invasion. Moreover, patients with higher MMP2 levels had markedly shorter overall survivals than those with low MMP2 levels. Multivariate analysis results suggested that the level of MMP2 expression is an independent prognostic indicator for the survival of patients with CRC. Silencing MMP2 expression in CRC cell lines with lentiviral-mediated shRNA markedly suppressed cell proliferation, colony formation, and invasion. Furthermore, we observed that vascular endothelial growth factor （VEGF） and membrane type 1 （MT1）-MMP protein levels were decreased in MMP2-down-regulated colorectal cells. Therefore, our study demonstrated that MMP2 is an important factor related to carcinogenesis and metastasis of CRC, and MMP2 promotes CRC cell growth and invasion by up-regulating VEGF and MT1-MMP expression, which makes this pathway a potential target for cancer treatment.