Title:Down-regulating Glypican-3 Expression: Molecular-targeted Therapy for Hepatocellular Carcinoma
VOLUME: 14 ISSUE: 14
Author(s):Zhizhen Dong, Min Yao, Li Wang, Junling Yang and Dengfu Yao
Affiliation:Center of Clinical Medicine, Affiliated Hospital of Nantong University, 20 West Temple Road, Nantong 226001, China.
Keywords:Diagnosis, glypican-3, hepatocellular carcinoma, signal pathways, targeted-therapy.
Abstract:Hepatocellular carcinoma (HCC) prognosis is very poor, its early treatment is of the utmost importance.
Glypican-3 (GPC-3), a membrane-associated heparan sulfate proteoglycan, plays a crucial role in cell proliferation and
metastasis, particularly in progression. GPC-3 mediated oncogenesis involves signaling pathways during the malignant
transformation of hepatocyte carcinogenesis, with an increasing expression of GPC-3 observed from non-cancerous- to
cancerous-tissues, with brown granule-like staining localized in tumor parts of atypical hyperplasia and HCC formation.
GPC-3 expression in HCC tissues or circulating blood was associated with tumor size or HBV infection. Circulation of
GPC-3-mRNA was detected in HCC patients with relation to TNM stage, periportal cancerous embolus, and extra-hepatic
metastasis. After hepatoma, cells were transfected with shRNA, GPC-3 expression or proliferation was inhibited with
promoting apoptosis, cell cycle arrested in G1 phase, alteration of hepatoma cell migration and invasion behaviors with
down-regulation of β-catenin, IGF-II, and VEGF, and growth of nude mice xenograft tumors was significantly suppressed
with the decreases in β -catenin, p-GSK3β, and cyclinD1 expression, suggesting that GPC-3 not only is a specific
biomarker for HCC diagnosis, but also is a valuable molecular-target for HCC gene therapy.
