Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.6.4 (chondroitinase)
 2,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two distinct classes of cell surface FGF-binding proteins have been identified. These receptors differ in both mode of interaction and in affinity for the FGFs. cDNAs that encode the low-affinity receptor were isolated from a hamster kidney cell line cDNA library by expression cloning. Transfected cells that contained these heparan sulfate proteoglycan FGF receptor cDNAs were enriched for by panning on basic FGF-coated plates. The analogous human cDNA was isolated from a hepatoma cell line cDNA library. The homology of our hamster cDNAs to the previously described murine integral membrane proteoglycan syndecan, together with an exact amino acid sequence match of our human-cDNA-encoded product to human syndecan, clearly indicates the identity of these independently isolated proteoglycans. Further confirmation that the expressed molecule serves as a proteoglycan core protein was achieved by immunoprecipitation of 35SO4-labeled material from solubilized transfected cells. Nitrous acid treatment and chondroitinase digestion revealed that 77% of the label was associated with heparan sulfate chains and 22% with chondroitin sulfate chains. These heparan sulfate chains contributed to the fivefold increase in the total heparan sulfate found to be present on the surface of the transfected cells compared with cells transfected with a vector lacking the cDNA insert.
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PMID:The molecular biology of heparan sulfate fibroblast growth factor receptors. 166 83

We have investigated the glycosaminoglycan composition of normal human liver, focal nodular hyperplasia, hepatic adenoma, and hepatocellular carcinoma. Uronic acid increased about 4 fold in the benign and reactive lesions, and greater than 7 fold in the carcinoma. Whereas in focal nodular hyperplasia and adenoma dermatan sulfate was the predominant glycosaminoglycan, in hepatocellular carcinoma chondroitin sulfate was the predominant species; it increased 24 fold over normal liver and 3-5 fold over all the other tissues. HPLC analysis of chondroitinase ABC or AC digests showed a 58 fold increase in Delta-Di-OS disaccharides in hepatocellular carcinoma, indicating significant undersulfation of chondroitin sulfate. Surprisingly, the normal-appearing liver surrounding the carcinoma showed glycosaminoglycan changes similar to adenoma and nodular hyperplasia. These results thus indicate that specific glycosaminoglycan changes occur in hepatocellular carcinoma, and suggest for the first time that proteoglycan metabolism is also altered in the non-cirrhotic, hepatic parenchyma adjacent to liver carcinoma.
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PMID:Altered glycosaminoglycan composition in reactive and neoplastic human liver. 215 32

In human hepatoma HepG2 cells, the serum inter-alpha-trypsin inhibitor (ITI)-like protein is synthesized from two protein precursors, the heavy chain (H) H2 and the light chain (L). Both of them carry sulphate groups involved in the chondroitin sulphate glycosaminoglycan (GAG) linkage, as demonstrated by [35S]sulphate labelling, chondroitinase digestion and inhibition with beta-D-xyloside, an artificial GAG acceptor. While inhibition of N-glycosylation prevented neither the maturation nor the secretion of the ITI-related entities, brefeldin A induced the accumulation of H and L precursors in the cells, therefore blocking subsequent association and maturation of the precursors before their secretion. The enzyme system involved in the ester linkage between H and L chains is localized in the trans-Golgi network since no ITI-like protein could be obtained in the presence of monensin; instead free heavy-chain protein forms and bikunin were secreted in culture supernatants. The ITI-like protein synthesized by HepG2 cells is therefore composed of two heavy chains HC2 linked to two bikunin chains by chondroitin sulphate bridges, although the GAG linkage between HC2 chains is presumably different. Further, a different maturation route leading to restricted heavy-chain forms, Hm and Hd, could be shown.
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PMID:Post-translational processing of the inter-alpha-trypsin inhibitor in the human hepatoma HepG2 cell line. 752 38

The biological activity of many cytokines is regulated by binding proteins present at the cell surface, in extracellular matrices or in soluble phase. We describe here a TGF-beta binding protein that is both an extracellular matrix and a cell surface protein. When intact extracellular matrices of HEP-G2 cells were affinity cross-linked with 125I-TGF-beta 1, two major binding components were seen: a 250-kD, proteoglycan-like molecule, presumed to be betaglycan, and a 60-kD protein. The 60-kD TGF-beta-binding protein was also present at the cell surface. It could be released from the cell surface by treating cells with high salt, heparin, chondroitin sulfate, heparitinase, or chondroitinase, indicating that it is bound to heparan sulfate and chondroitin sulfate proteoglycans. The 60-kD protein bound TGF-beta 1 with an apparent dissociation constant of 1.6 nM, and there were 30,000 binding sites per cell at the cell surface. In addition to the HEP-G2 cells and another hepatoma cell line, the 60-kD protein was also found in a human colon carcinoma (HT-29) cell line but not in rat kidney (NRK-49F) or human fibroblast (HUT-12) cell lines. The 60-kD protein could be extracted from cells containing it and transferred to the surface of previously negative cells. The 60-kD protein may serve to regulate the binding of TGF-beta to its signal transducing receptors by targeting TGF-beta to appropriate locations in the microenvironment of cells.
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PMID:A 60-kD protein mediates the binding of transforming growth factor-beta to cell surface and extracellular matrix proteoglycans. 833 95

The level of sulfo-Lea (SO3-3Gal beta 1-3(Fuc alpha 1-4)GlcNAc) epitope recognized by monoclonal antibody (mAb) 91.9H in hepatic metastasis of colon carcinoma is known to be lower than at the primary sites. We examined 19 human colon carcinoma cell lines for their production of this epitope. Sixteen cell lines were found to produce high M(r) components that metabolically incorporated [35S]sulfate and were resistant to heparitinase I and chondroitinase ABC, and 8 of them were reactive with mAb 91.9H as shown by western blotting analysis. These were all of the 4 cell lines derived from well differentiated primary tumors (HCCP-2998, LS174T, GEO, and CBS), 2 of 10 cell lines (DLD-1 and HCT116) from moderately to poorly differentiated primary tumors, and 2 of 5 cell lines (SW480 and HCC-M1544) from metastases. Incubation of LS174T cells with benzyl-N-acetyl-alpha-D-galactosaminide abrogated the incorporation of [35S]sulfate and the reactivity of mAb 91.9H with high M(r) components in the cell lysates. Sodium chlorate, which inhibits the formation of 3'-phosphoadenosine 5'-phosphosulfate, also inhibited the [35S]sulfate incorporation and reactivity with mAb 91.9H. These treatments did not change the incorporation of [14C]threonine into high M(r) components. These results indicated that sulfo-Lea epitopes were expressed on O-linked carbohydrate chains in sulfomucins. Immunohistochemical studies of tumor tissues in nude mice indicated that sulfo-Lea was expressed at the site of orthotopic transplantation in the cecum. The expression appeared to be suppressed in liver metastatic foci in nude mice.
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PMID:Expression of mucin-associated sulfo-Lea carbohydrate epitopes on human colon carcinoma cells. 1008 87