Overexpression of angiopoietin-1 and angiopoietin-2 in hepatocellular carcinoma

J Hepatol. 2004 May;40(5):799-807. doi: 10.1016/j.jhep.2004.01.027.


Background/aims: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiopoietin-1 / genetics*
  • Angiopoietin-1 / metabolism*
  • Angiopoietin-2 / genetics*
  • Angiopoietin-2 / metabolism*
  • Base Sequence
  • Carcinoma, Hepatocellular / blood supply
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / blood supply
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Receptor, TIE-2 / metabolism*


  • ANGPT1 protein, human
  • Angiopoietin-1
  • Angiopoietin-2
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptor, TIE-2