Cyclophilin A promotes human hepatocellular carcinoma cell metastasis via regulation of MMP3 and MMP9

• DOI: 10.1007/s11010-011-0909-z
• Publication Date: 2011-06-10T13:30:33Z
• Authors: Mingjun Zhang; Chun Dai; Hengrui Zhu; Shuai Chen; Yanhua Wu; Qiang Li; Xianzhuo Zeng; Wenzhang Wang; Jie Zuo; Mei Zhou; Zongjun Xia; Guoqing Ji; Hexige Saiyin; Lunxiu Qin; Long Yu
• Keywords: 0301 basic medicine; Carcinoma, Hepatocellular; Liver Neoplasms; Mice, Nude; Microarray Analysis; 3. Good health; Gene Expression Regulation, Neoplastic; Mice; 03 medical and health sciences; Matrix Metalloproteinase 9; Cell Line, Tumor; Cell Adhesion; Animals; Humans; Matrix Metalloproteinase 3; Neoplasm Invasiveness; Neoplasm Metastasis; Cyclophilin A; Cell Proliferation

Cyclophilin A (CypA) is a member of peptidyl prolyl isomerases (PPIases), which catalyze the cis/trans isomerization of prolyl peptide bonds on the NH-terminal side of Pro residues in peptide chains. Altered expression of CypA has been reported in hepatocellular carcinoma (HCC), but the biological functions of CypA in HCC remain unknown. We found that the level of CypA expression correlated with the metastatic capability of two HCC cell lines, MHCC97-L and MHCC97-H. Stable expression of ectopic CypA in SK-Hep1 cells promotes cell adhesion, motility, chemotaxis, and in vivo lung metastasis, without affecting cell proliferation. We further analyzed microarray results to identify target genes controlled by CypA. Twenty-one genes related to metastasis were altered by CypA over-expression. A member of matrix metalloproteinase, MMP3, was identified by microarray analysis. The regulation of MMP3 and its homologue MMP9 by CypA were further confirmed by quantitative real-time RT-PCR and zymography assay. Taken together, our data suggest that CypA promotes HCC cell metastasis at least partially through up-regulation of MMP3 and MMP9.