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

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. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.