Overexpression of angiopoietin-1 and angiopoietin-2 in hepatocellular carcinoma.
OBJECTIVE
Hepatocellular carcinoma (HCC) is a highly vascular tumor. Angiopoietin-1 and Angiopoietin-2 have been shown to be involved in tumor angiogenesis. We investigated the expression of Angiopoietin-1 and Angiopoietin-2 in HCC.


METHODS
The expression of Angiopoietin-1 and Angiopoietin-2 mRNAs in cultured hepatoma cells under hypoxic conditions and in HCC and noncancerous liver tissue was evaluated by real-time PCR. The expression of Angiopoietin-1, Angiopoietin-2, and their receptor Tie-2 in HCC was assessed by immunohistochemistry. The changes in Angiopoietin-1 and Angiopoietin-2 expression were evaluated in relation to tumor differentiation and changes in tumor vascularity.


RESULTS
Hypoxic conditions did not up-regulate the expression of Angiopoietin-1 and Angiopoietin-2 mRNAs in hepatoma cells. Increased expression of Angiopoietin-1 and Angiopoietin-2 mRNAs was detected in HCC. Angiopoietin-1 and Angiopoietin-2 were detected in hepatoma cells, hepatic stellate cells, and smooth muscle cells, whereas Tie-2 was detected in endothelial cells, hepatic stellate cells and smooth muscle cells. Increased expression of Angiopoietin-2 and Angiopoietin-2 mRNA was associated with tumor dedifferentiation. The expression of Angiopoietin-1 and Angiopoietin-2 correlated with HCC vascularity.


CONCLUSIONS
Our findings indicate that the increased expression of Angiopoietin-1 and Angiopoietin-2 play a critical role in the process of vascular development in HCC.
Torimura
Takuji
T
Second Department of Medicine, Kurume University School of Medicine, Liver Cancer Division, Research Center for Innovative Cancer Therapy, and Center of the 21st Century COE Program for Medical Science, Kurume University, Fukuoka 830-0011, Japan.
Ueno
Takato
T
Kin
Motoaki
M
Harada
Riko
R
Taniguchi
Eitaro
E
Nakamura
Toru
T
Sakata
Ryuichiro
R
Hashimoto
Osamu
O
Sakamoto
Masaharu
M
Kumashiro
Ryukichi
R
Sata
Michio
M
Nakashima
Osamu
O
Yano
Hirohisa
H
Kojiro
Masamichi
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042683:Angiopoietin-1 / Q000235:genetics* / Q000378:metabolism*; D042702:Angiopoietin-2 / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000378:metabolism*
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D042787:Receptor, TIE-2