Heparan sulphate proteoglycan expression in human primary liver tumours

Abstract

Heparan sulphate proteoglycans (HSPGs) play important biological roles in cell-matrix adhesion processes and are essential regulators of growth factor actions (e.g., as co-receptor for hepatocyte growth factor). Since in liver carcinogenesis, interactions between cells, the matrix, and growth factors play a major role, the aim of this study was to investigate whether the distribution pattern of HSPGs is altered in human primary liver tumours. Twenty-two primary liver tumours and five normal liver biopsies were studied, using specific monoclonal antibodies against syndecans-1, -2, -3, and -4; glypican; perlecan; and heparan sulphate chains. Cholangiocarcinomas as well as hepatocellular carcinomas showed an altered immunoreactivity pattern of the different HSPGs in comparison with normal liver parenchyma, probably reflecting the growth regulatory roles of HSPGs. Intracellular positivity for integral membrane HSPGs syndecan-1 and especially syndecan-4 was a constant finding in most tumours, suggesting increased synthesis or internalization of these HSPGs. Syndecan-3 and perlecan expression in tumours was found in an expected distribution pattern. The strong reactivity for syndecan-3 and perlecan in tumoral stromal vessels might suggest a role for these HSPGs in tumoral angiogenesis. In addition, perlecan probably exerts its known growth factor reservoir function also in the stroma of primary liver tumours.