title: Quantitative and qualitative alterations of heparan sulfate in fibrogenic liver diseases and hepatocellular cancer.
abstract: Heparan sulfate (HS), due to its ability to interact with a multitude of HS-binding factors, is involved in a variety of physiological and pathological processes. Remarkably diverse fine structure of HS, shaped by non-exhaustive enzymatic modifications, influences the interaction of HS with its partners. Here we characterized the HS profile of normal human and rat liver, as well as alterations of HS related to liver fibrogenesis and carcinogenesis, by using sulfation-specific antibodies. The HS immunopattern was compared with the immunolocalization of selected HS proteoglycans. HS samples from normal liver and hepatocellular carcinoma (HCC) were subjected to disaccharide analysis. Expression changes of nine HS-modifying enzymes in human fibrogenic diseases and HCC were measured by quantitative RT-PCR. Increased abundance and altered immunolocalization of HS was paralleled by elevated mRNA levels of HS-modifying enzymes in the diseased liver. The strong immunoreactivity of the normal liver for 3-O-sulfated epitope further increased with disease, along with upregulation of 3-OST-1. Modest 6-O-undersulfation of HCC HS is probably explained by Sulf overexpression. Our results may prompt further investigation of the role of highly 3-O-sulfated and partially 6-O-desulfated HS in pathological processes such as hepatitis virus entry and aberrant growth factor signaling in fibrogenic liver diseases and HCC.
authors.affiliation: Second Department of Pathology, Semmelweis University, 93 Ulloi út H-1091 Budapest, Hungary. peter.tatrai@biomembrane.hu
authors.forename: Péter
authors.initials: P
authors.lastname: Tátrai
authors.forename: Krisztina
authors.initials: K
authors.lastname: Egedi
authors.forename: Aron
authors.initials: A
authors.lastname: Somorácz
authors.forename: Toin H
authors.initials: TH
authors.lastname: van Kuppevelt
authors.forename: Gerdy
authors.initials: G
authors.lastname: Ten Dam
authors.forename: Malcolm
authors.initials: M
authors.lastname: Lyon
authors.forename: Jon A
authors.initials: JA
authors.lastname: Deakin
authors.forename: András
authors.initials: A
authors.lastname: Kiss
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Schaff
authors.forename: Ilona
authors.initials: I
authors.lastname: Kovalszky
mesh_terms: D018171:Agrin / Q000096:biosynthesis; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002908:Chronic Disease; D004187:Disaccharides / Q000378:metabolism; D020518:Focal Nodular Hyperplasia / Q000378:metabolism; D005966:Glucuronidase / Q000096:biosynthesis / Q000235:genetics; D053673:Glypicans / Q000096:biosynthesis; D019812:Heparan Sulfate Proteoglycans / Q000096:biosynthesis; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015238:Sulfotransferases / Q000096:biosynthesis / Q000235:genetics; D053668:Syndecan-1 / Q000096:biosynthesis; D000099175:Heparanase
chemical_list: D018171:Agrin; D004187:Disaccharides; D005966:Glucuronidase; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D012333:RNA, Messenger; D015238:Sulfotransferases; D053668:Syndecan-1; D000099175:Heparanase; C071927:perlecan