Association of glypican-3 expression with growth signaling molecules in hepatocellular carcinoma.
OBJECTIVE
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 beta-catenin.


CONCLUSIONS
These results suggest that GPC3, in conjunction with MMPs and growth signaling molecules, might play an important role in the progression of HCC.
Akutsu
Noriyuki
N
First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
Yamamoto
Hiroyuki
H
Sasaki
Shigeru
S
Taniguchi
Hiroaki
H
Arimura
Yoshiaki
Y
Imai
Kohzoh
K
Shinomura
Yasuhisa
Y
D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D053673:Glypicans / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D013429:Sulfatases; D015238:Sulfotransferases / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
D053673:Glypicans; D036341:Intercellular Signaling Peptides and Proteins; D051153:Wnt Proteins; C470791:SULF1 protein, human; D015238:Sulfotransferases; C470792:SULF2 protein, human; D013429:Sulfatases; D020782:Matrix Metalloproteinases