Heparanase expression in hepatocellular carcinoma and the cirrhotic liver.

The endoglycosidase heparanase plays an important role in tumor cell invasion, angiogenesis and metastasis. In this study, we analyzed heparanase expression in primary hepatocellular carcinoma (HCC), liver cirrhosis and normal liver tissues to further evaluate its role in tumor pathogenesis. Heparanase mRNA expression was measured by real-time quantitative RT-PCR and localized at the cellular level by in situ hybridization. Heparanase protein levels and its localization were determined by Western blotting and immunohistochemistry. Expression of heparanase mRNA in primary HCC was increased 2-fold compared with liver cirrhosis and 2.2-fold in comparison with normal liver tissues, and this overexpression was even more pronounced in advanced stage HCC. In contrast, heparanase expression levels between cirrhotic tissues and normal liver tissues were not significantly different. In HCC the increased heparanase expression was localized in hepatic tumor cells and was only weakly present or absent in normal hepatocytes, bile duct epithelial cells and the connective tissues. These results suggest that increased heparanase expression is involved in the pathogenesis and progression of HCC. Its specific up-regulation in HCC but not in liver cirrhosis indicates that it might be used as a molecular marker for the differentiation of these disorders.