title: Association of glypican-3 expression with growth signaling molecules in hepatocellular carcinoma.
abstract: 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.
authors.affiliation: First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Akutsu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sasaki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Arimura
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Imai
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Shinomura
mesh_terms: 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
chemical_list: 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