Expression of ephrin-B1 in hepatocellular carcinoma: possible involvement in neovascularization.
OBJECTIVE
Hepatocellular carcinoma (HCC) is, in general, a hypervascular tumor. Ephrin/Eph molecules have recently been reported as possible regulators of angiogenesis. We aimed to clarify the role of ephrin-Bs (B1-B3) in the progression of HCC.


METHODS
Ephrin-Bs transcripts in 26 HCC and their corresponding non-tumor liver tissues were analyzed by the quantitative reverse transcription-polymerase chain reaction. We established ephirn-B1 overexpressing cell in a human HCC cell line, PLC/PRF/5 cell, and their in vivo growth monitored after subcutaneous injection into nude mice. Neovascularization in the inoculated tumors was evaluated by the immunohistochemical staining of CD31. The migration and proliferation of human umbilical vein endothelial cells (HUVECs) in response to soluble ephrin-B1-Fc was examined.


RESULTS
The expression of the ephrin-B1 transcript but not -B2 and -B3 transcripts was significantly higher in HCC tissues than in non-tumor tissues (P<0.05). The ephrin-B1 overexpressing cells developed tumors more rapidly than controls in vivo (P<0.05), although in vitro cell growth was not affected. The tumor vessel number significantly increased in the ephrin-B1 overexpressing tumors (P<0.0001). In addition, in vitro studies revealed that ephrin-B1 induced migration and proliferation of HUVECs.


CONCLUSIONS
Ephrin-B1 may be involved in in vivo tumor progression by promoting neovascularization in HCC.
Sawai
Yoshiyuki
Y
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Tamura
Shinji
S
Fukui
Koji
K
Ito
Nobuyuki
N
Imanaka
Kazuho
K
Saeki
Ayuko
A
Sakuda
Shigeru
S
Kiso
Shinichi
S
Matsuzawa
Yuji
Y
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000503:physiopathology*; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000166:cytology; D036387:Ephrin-B1 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D014471:Umbilical Veins / Q000166:cytology
D036387:Ephrin-B1