Original Article
Copyright ©2010 Baishideng. All rights reserved.
World J Gastroenterol. Jul 28, 2010; 16(28): 3521-3528
Published online Jul 28, 2010. doi: 10.3748/wjg.v16.i28.3521
Association of glypican-3 expression with growth signaling molecules in hepatocellular carcinoma
Noriyuki Akutsu, Hiroyuki Yamamoto, Shigeru Sasaki, Hiroaki Taniguchi, Yoshiaki Arimura, Kohzoh Imai, Yasuhisa Shinomura
Noriyuki Akutsu, Hiroyuki Yamamoto, Shigeru Sasaki, Hiroaki Taniguchi, Yoshiaki Arimura, Yasuhisa Shinomura, First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan
Kohzoh Imai, Sapporo Medical University, Sapporo 060-8556, Japan
Author contributions: Akutsu N and Yamamoto H designed the research; Akutsu N, Yamamoto H, Sasaki S, Taniguchi H and Arimura Y performed the research; Akutsu N, Yamamoto H, Imai K and Shinomura Y analyzed the data; Akutsu N, Yamamoto H and Shinomura Y wrote the paper.
Supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to Yamamoto H, Imai K and Shinomura Y) and Grants-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare of Japan (to Yamamoto H)
Correspondence to: Hiroyuki Yamamoto, MD, FJSIM, PhD, First Department of Internal Medicine, Sapporo Medical University School of Medicine, S.-1, W.-16, Chuo-ku, Sapporo 060-8543, Japan. h-yama@sapmed.ac.jp
Telephone: +81-11-6112111 Fax: +81-11-6112282
Received: January 25, 2010
Revised: April 6, 2010
Accepted: April 13, 2010
Published online: July 28, 2010
Abstract

AIM: To clarify the association of glypican-3 (GPC3) expression with Wnt and other growth signaling molecules in hepatocellular carcinoma (HCC).

METHODS: Expression of GPC3, Wnt, matrix metalloproteinases (MMPs), sulfatase (SULF)1, SULF2, and other growth signaling molecules was analyzed in HCC cell lines and tissue samples by real-time reverse transcription-polymerase chain reaction, immunoblotting, and/or immunostaining. Expression of various genes in GPC3 siRNA-transfected HCC cells was analyzed.

RESULTS: GPC3 was overexpressed in most HCCs at mRNA and protein levels and its serum levels were significantly higher in patients with HCC than in non-HCC subjects (P < 0.05). Altered expressions of various MMPs and growth signaling molecules, some of which were correlated with GPC3 expression, were observed in HCCs. Down-regulation of GPC3 expression by siRNA in GPC3-overexpressing HCC cell lines resulted in a significant decrease in expressions of MMP2, MMP14, fibroblast growth factor receptor 1, insulin-like growth factor 1 receptor. GPC3 expression was significantly correlated with nuclear/cytoplasmic localization of β-catenin.

CONCLUSION: These results suggest that GPC3, in conjunction with MMPs and growth signaling molecules, might play an important role in the progression of HCC.

Keywords: Glypican-3, Wnt, Matrix metalloproteinases, Sulfatase, Hepatocellular carcinoma