Association of glypican-3 expression with growth signaling molecules in hepatocellular carcinoma

作者：Akutsu Noriyuki; Yamamoto Hiroyuki^*; Sasaki Shigeru; Taniguchi Hiroaki; Arimura Yoshiaki; Imai Kohzoh; Shinomura Yasuhisa

来源：World Journal of Gastroenterology, 2010, 16(28): 3521-3528.

DOI：10.3748/wjg.v16.i28.3521

• Glypican-3
• Wnt
• Matrix metalloproteinases
• Sulfatase
• Hepatocellular carcinoma

AIM: To clarify the association of glypican-3 (GPO) ex-pression 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 beta-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.

• 出版日期2010-7-28