REDUCED EXPRESSION OF SYNDECAN-1 IN HUMAN HEPATOCELLULAR-CARCINOMA WITH HIGH METASTATIC POTENTIAL

Syndecans comprise a gene family of transmembrane proteoglycans that r egulate cellular behavior through interactions with various effecters, including heparin-binding growth factors and insoluble matrix compone nts. Syndecan-1, the most extensively studied, localizes in epithelial cells and has been shown to present in normal hepatocytes. However, l ittle is known about the change of syndecan-1 expression in human hepa tocellular carcinoma (HCC). We investigated syndecan-1-protein express ion by immunohistochemistry in 57 HCC tissue samples. Syndecan-1 gene expression was also determined. Syndecan-1 protein was expressed in cy toplasm and cell membrane of the hepatocytes and in the bile duct epit helial cells of liver with underlying hepatitis and cirrhosis. Convers ely, among 57 HCC tissues, 39 HCC (68.4%) showed negative staining; 50 % of well-differentiated HCC showed positive staining, whereas 82.4% o f poorly differentiated HCC were negative. Loss of syndecan-1-protein expression was more prevalent in HCC with intra-hepatic metastasis (85 .2%) than those without metastasis (48.0%). Similarly, syndecan-1 expr ession was significantly reduced in HCC with extrahepatic metastasis ( 91.7%) as compared with the HCC without extra-hepatic metastasis (62.2 %). The gene expression of syndecan-1 was significantly lower in HCC t issue than that in non-tumoral liver tissue. In 2 human HCC cell lines with poorly differentiated phenotype, HLE and HLF, syndecan-1 express ion was markedly decreased both at the mRNA and the protein levels. Th ese results suggest that the loss of syndecan-I expression is a charac teristic feature of HCC with high metastatic potential. (C) 1997 Wiley -Liss, Inc.