Initial study of invasion and metastasis in hepatocellular carcinoma regulated by glypican 3

Abstract

Objective To investigate the role of GPC3 in invasion and metastasis of hepatocelluar carcinoma (HCC). Methods SiRNA targeting GPC3 mRNA was transfected into Hep3B and HepG2 cell lines. Recombinant lentiviral vector containing GPC3 gene was constructed and transfected into SMMC-7721 and SK-HEP-1. The expressions of epithelial-mesenchymal transition (EMT) markers (N-Cadherin, E-Cadherin, SNAIL, Vimentin) and metaproteinases (MMP)-2, MMP-3, MMP-7 were detected by Western blotting and qPCR. Results The ability of migration and invasion of those with GPC3 high expression was higher than those with low GPC3 expression (P<0.05). The occurrence of metastasis was higher in those with GPC3 high expression in mice orthotopic HCC model compared with low GPC3 expression (P<0.05). Over-expression of GPC3 up-regulated N-cadherin expression and inhibited E-cadherin, whereas, interference GPC3 expression by siRNA targeted GPC3 inhibited N-cadherin expression and upregulated E-cadherin expression. Furthermore, over-expression of GPC3 up-regulated MMP-2, MMP-3, MMP-7 expression in SMMC-7721 and SK-HEP-1 cell lines (P<0.05). Conclusion GPC3 promotes HCC cell migration and invasion through inducing EMT and up-regulation of MMPs expression. Key words: Carcinoma, hepatocellular; Glypicans; Neoplasm invasiveness; Neoplasm metastasis; Epithelial-mesenchymal transition