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ID 52020
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Author
Kataoka, Jyunro
Iwamuro, Masaya
Horiguchi, Shigeru
Nishina, Shin-ichi
Takaoka, Nobuyuki
Uemura, Masayuki
Kobayashi, Yoshiyuki
Abstract
Background and Aim: Hepatocellular carcinoma (HCC) is a hypervascular tumor, and angiogenesis plays an important role in its development. Previously, we demonstrated that des-gamma-carboxyl prothrombin (DCP) promotes both cell proliferation and migration of human umbilical vein endothelial cells (HUVECs) by inducing the autophosphorylation of kinase insert domain receptor (KDR). In the present study, DCP-associated tumor angiogenesis was assessed by comparing hypovascular and common hypervascular HCC. Methods: The solitary HCCs of 827 patients were classified into two groups according to the tumor density at the arterial phase of a dynamic computed tomography scan; the initial clinical data of patients with the hyper- and hypovascular types were compared. The HCC tissues from 95 tumors were analyzed by immunohistochemical staining for DCP and phosphorylated KDR, and intratumoral microvessel density (MVD) was analyzed to evaluate microvessel angiogenesis. Results: The serum DCP levels (320 +/- 3532 mAU/mL) and tumor size (18.4 +/- 9.0 mm) of patients with hypervascular HCC were significantly greater than those with hypovascular HCC (38.7 +/- 80 mAU/mL and 14.6 +/- 5.2 mm, P < 0.001). Immunohistochemical analysis revealed that the expressions of DCP and phospho-KDR were significantly greater in hypervascular HCC (71.4% and 31.0%, respectively) than in hypovascular HCC (7.6% and 5.7%, respectively). Intratumoral MVD was significantly correlated with DCP (r = 0.48, P < 0.0001). Conclusions: des-gamma-carboxyl prothrombin production is associated with tumor angiogenesis in HCC.
Keywords
des-gamma-carboxyl prothrombin
hepatocellular carcinoma
intratumoral microvessel density
kinase insert domain receptor
Published Date
2012-10
Publication Title
Journal of Gastroenterology and Hepatology
Volume
volume27
Issue
issue10
Start Page
1602
End Page
1608
ISSN
0815-9319
Content Type
Journal Article
Official Url
http://dx.doi.org/10.1111/j.1440-1746.2012.07173.x
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/51951
language
英語
File Version
author
Refereed
True
DOI
Web of Sience KeyUT