Heparanase expression in gastrointestinal malignancies.

Abstract

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In this study, we examined the distribution of heparanase protein in 75 esophageal squamous cell carcinomas,44 gastric carcinomas and 54 colon carcinomas by immunohistochemistry and analyzed the relationship between heparanase expression and clinicopathological characteristics. In situ hybridization showed that the mRNA expression pattern of heparanase was similar to that of the protein, suggesting that increased expression of the heparanase protein at the invasive front was caused by an increase of heparanase mRNA in tumor cells. Heparanase expression correlated significantly with clinicopathological parameters,such as depth of invasion, lymphnode metastasis,lymphatic invasion and TNM stage.Overexpression of heparanase in gastrointestinal malignanciess was also associated with poor survival.In addition, we evaluated microvessel density (MVD) by Factor VIII staining to confirm with the relationship between heparanase and tumor angiogenesis. Furthermore we transfected heparanase cDNA into RPMI 4788 colon cancer cell line and performed invasion assay. Heparanase transfected RPMI 4788 showed significantly higher migration activity in comparison with mock. Moreover heparanase inhibitor significantly surpressed the migration ability. Our results suggest that heparanase appears to be a useful prognostic factor for gastrointestinal malignancies. The inhibition of heparanase activity may provide a rational treatment, which controls tumor angiogenesis, invasion and metastasis.