title: Overexpression of angiopoietin-1 and angiopoietin-2 in hepatocellular carcinoma.
abstract: 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.
authors.affiliation: 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.
authors.forename: Takuji
authors.initials: T
authors.lastname: Torimura
authors.forename: Takato
authors.initials: T
authors.lastname: Ueno
authors.forename: Motoaki
authors.initials: M
authors.lastname: Kin
authors.forename: Riko
authors.initials: R
authors.lastname: Harada
authors.forename: Eitaro
authors.initials: E
authors.lastname: Taniguchi
authors.forename: Toru
authors.initials: T
authors.lastname: Nakamura
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Sakata
authors.forename: Osamu
authors.initials: O
authors.lastname: Hashimoto
authors.forename: Masaharu
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Ryukichi
authors.initials: R
authors.lastname: Kumashiro
authors.forename: Michio
authors.initials: M
authors.lastname: Sata
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakashima
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Yano
authors.forename: Masamichi
authors.initials: M
authors.lastname: Kojiro
mesh_terms: 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*
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D042787:Receptor, TIE-2