Requisite role of VEGF receptors in angiogenesis of hepatocellular carcinoma: a comparison with angiopoietin/Tie pathway.
BACKGROUND
Tumor vascularity is an independent predictor of prognosis in HCC patients, however, the growth factors governing the angiogenesis remain obscure.


METHODS
Multiple mRNA species of angiogenesis-related growth factors/receptors and CD31 were evaluated in 38 hepatocellular carcinomas (HCCs) and surrounding livers (SL) by a highly sensitive RNase protection assay.


RESULTS
Significant increases in VEGF, VEGFR3, endoglin and CD31 mRNA expressions were noted in HCC rather than in SL. Only VEGFR1 had significant correlation with CD31 expression. VEGFRs and CD31 overexpressed in tumors with portal vein invasion and only VEGFR3- and CD31-positive patients had significantly shorter disease-free survival. Tie1 and Tie2 were overexpressed in large HCCs. The VEGF and Tie receptors expressed differentially in 28 tumors.


CONCLUSIONS
The VEGF receptors might play the major role in HCC angiogenesis and prognosis. The differential expression of receptors might prove valuable in selected subsets of patients for tailored antiangiogenic therapy in HCC patients.
Dhar
Dipok Kumar
DK
Second Department of Surgery, Shimane Medical University, Izumo, Japan. nigeka33@shimane-med.ac.jp
Naora
Hiroyuki
H
Yamanoi
Akira
A
Ono
Takashi
T
Kohno
Hitoshi
H
Otani
Hiroki
H
Nagasue
Naofumi
N
D042683:Angiopoietin-1; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D042810:Receptor, TIE-1; D017978:Receptors, Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D042764:Receptors, TIE; D040262:Receptors, Vascular Endothelial Growth Factor
D042683:Angiopoietin-1; D008562:Membrane Glycoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D042810:Receptor, TIE-1; D042764:Receptors, TIE; D040262:Receptors, Vascular Endothelial Growth Factor