Quantitative and qualitative alterations of heparan sulfate in fibrogenic liver diseases and hepatocellular cancer.

2.50
Hdl Handle:
http://hdl.handle.net/10541/109396
Title:
Quantitative and qualitative alterations of heparan sulfate in fibrogenic liver diseases and hepatocellular cancer.
Authors:
Tátrai, Péter; Egedi, Krisztina; Somorácz, Aron; Van Kuppevelt, Toin H; Ten Dam, Gerdy; Lyon, Malcolm; Deakin, Jon A; Kiss, András; Schaff, Zsuzsa; Kovalszky, Ilona
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.
Affiliation:
Second Department of Pathology, Semmelweis University, 93 Ulloi út H-1091 Budapest, Hungary. peter.tatrai@biomembrane.hu
Citation:
Quantitative and qualitative alterations of heparan sulfate in fibrogenic liver diseases and hepatocellular cancer. 2010, 58 (5):429-41 J. Histochem. Cytochem.
Journal:
The Journal of Histochemistry and Cytochemistry
Issue Date:
May-2010
URI:
http://hdl.handle.net/10541/109396
DOI:
10.1369/jhc.2010.955161
PubMed ID:
20124094
Type:
Article
Language:
en
ISSN:
1551-5044
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorTátrai, Péteren
dc.contributor.authorEgedi, Krisztinaen
dc.contributor.authorSomorácz, Aronen
dc.contributor.authorVan Kuppevelt, Toin Hen
dc.contributor.authorTen Dam, Gerdyen
dc.contributor.authorLyon, Malcolmen
dc.contributor.authorDeakin, Jon Aen
dc.contributor.authorKiss, Andrásen
dc.contributor.authorSchaff, Zsuzsaen
dc.contributor.authorKovalszky, Ilonaen
dc.date.accessioned2010-08-10T11:09:38Z-
dc.date.available2010-08-10T11:09:38Z-
dc.date.issued2010-05-
dc.identifier.citationQuantitative and qualitative alterations of heparan sulfate in fibrogenic liver diseases and hepatocellular cancer. 2010, 58 (5):429-41 J. Histochem. Cytochem.en
dc.identifier.issn1551-5044-
dc.identifier.pmid20124094-
dc.identifier.doi10.1369/jhc.2010.955161-
dc.identifier.urihttp://hdl.handle.net/10541/109396-
dc.description.abstractHeparan 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.en
dc.language.isoenen
dc.subjectLiver Canceren
dc.subject.meshAgrin-
dc.subject.meshAnimals-
dc.subject.meshCarcinoma, Hepatocellular-
dc.subject.meshChronic Disease-
dc.subject.meshDisaccharides-
dc.subject.meshFocal Nodular Hyperplasia-
dc.subject.meshGlucuronidase-
dc.subject.meshGlypicans-
dc.subject.meshHeparan Sulfate Proteoglycans-
dc.subject.meshHeparitin Sulfate-
dc.subject.meshHumans-
dc.subject.meshImmunohistochemistry-
dc.subject.meshLiver-
dc.subject.meshLiver Cirrhosis-
dc.subject.meshLiver Neoplasms-
dc.subject.meshMale-
dc.subject.meshRNA, Messenger-
dc.subject.meshRats-
dc.subject.meshRats, Wistar-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.subject.meshSulfotransferases-
dc.subject.meshSyndecan-1-
dc.titleQuantitative and qualitative alterations of heparan sulfate in fibrogenic liver diseases and hepatocellular cancer.en
dc.typeArticleen
dc.contributor.departmentSecond Department of Pathology, Semmelweis University, 93 Ulloi út H-1091 Budapest, Hungary. peter.tatrai@biomembrane.huen
dc.identifier.journalThe Journal of Histochemistry and Cytochemistryen

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.