Tie2 vascular endothelial receptor expression and function in hepatocellular carcinoma

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<jats:sec> <jats:title/> <jats:p>Hepatocellular carcinoma (HCC) is generally characterized as a hypervascular tumor of rapid growth. We have previously reported that angiopoietin (Ang), a ligand for Tie2 vascular endothelial-specific receptor tyrosine kinase, may play a role in the progression of human HCC (J Clin Invest 1999;103:341-345) and matrix proteinase expression (Cancer Res 2001;61:2145-2153). However, the role of Tie2 receptor in hepatic oncogenesis is unknown. The Tie2 receptor protein was overexpressed in the neovascular endothelium of 31 of 39 (80%) human HCC tumors by immunohistochemical analysis with significant correlation to cell dedifferentiation and tumor size (<jats:italic toggle="yes">P</jats:italic> < .05). <jats:italic toggle="yes">In vitro</jats:italic> expression of a dominant-negative construct, containing a soluble Tie2 ectodomain (sTie2), led to Ang protein interaction, inhibition of endogenous Tie2 phosphorylation in vascular endothelial cells and matrix metalloproteinase 9 (MMP-9) suppression. In conclusion, tumorigenicity with neovascularization was suppressed by <jats:italic toggle="yes">in vivo</jats:italic> gene transfer and sTie2 expression in a murine HCC model, suggesting a possible role for Tie2 expression in the induction of HCC neovascularization and disease progression. Inhibition of the Ang/Tie2 signal transduction cascade is a promising approach for tumor treatment.</jats:p> </jats:sec>

Journal

  • Hepatology

    Hepatology 35 (4), 861-867, 2002-04

    Ovid Technologies (Wolters Kluwer Health)

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