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)

Since the 1960s, the loss of sulfomucin from colonic epithelium has been considered to be an indicator of an early stage of carcinogenesis; yet, the biochemical basis for this phenomenon has never been elucidated. We recently prepared a monoclonal antibody (mAb) 91.9H that immunoprecipitates the normal colonic mucins metabolically incorporating [35S]-sulfate. This mouse IgG1 antibody did not cross-react with colon carcinoma mucins that lack sulfate groups. Using normal colonic epithelia unlabeled or radiolabeled with [35S]sulfate and [3H]glucosamine, we purified a high molecular weight glycoprotein that reacts with mAb 91.9H. This was achieved by a combination of DEAE-cellulose anion-exchange chromatography, consecutive treatments with chondroitinase ABC plus heparitinase and with sodium dodecyl sulfate plus 2-mercaptoethanol, and gel filtration on Sepharose CL-2B in the presence of 8 M urea. Antibody reactivity was found in acidic but not neutral high molecular weight glycoproteins. After Sepharose CL-2B fractionation, the mAb 91.9H-reactive fractions consisted of a component with an approximate molecular weight of 500,000-900,000. A purified sulfomucin contained protein, neutral sugar, amino sugar, sialic acid, and sulfate in an approximate ratio of 2.5:1.0:1.1:0.4:0.5. The polypeptide portion was rich in hydrophilic amino acids, particularly threonine. Binding of mAb 91.9H in solid-phase assays was inhibited to 50% by purified normal colon acidic mucin at doses of 5-50 micrograms/ml, depending on different preparations. Various glycosaminoglycans or sulfatides did not show inhibitory activity. Sulfomucin reactivity with mAb 91.9H, as determined by solid-phase-binding inhibition and by dot blot assays, was significantly reduced by chemical desulfation of sulfomucins with anhydrous hydrochloric acid, suggesting that sulfate groups served as a portion of the immunochemical determinant for this antibody. Sulfate residues were apparently linked to alkaline-sensitive carbohydrate chains, but alkaline-released carbohydrate chains did not react with mAb 91.9H. Immunohistochemical examinations showed that mAb 91.9H bound normal colonic epithelial cells, which also stained with high-iron diamine, more strongly than it bound colon carcinoma cells.
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PMID:Human colonic sulfomucin identified by a specific monoclonal antibody. 191 91

Urinary excretion of trypsin inhibitor increased after injection of a carcinogen, N-nitrosobis(2-oxopropyl)amine, into Syrian hamsters. Two inhibitors were purified to apparent homogeneity from urine collected during the course of the carcinogenesis experiment. Their complete amino acid sequences were determined by Edman degradation of the intact proteins and partially degraded fragments. One corresponded to a hamster liver cDNA clone that hybridized with human bikunin probe [Ide et al, (1994) Biochim, Biophys. Acta 1209, 286-292], except that the protein sequence lacked C-terminal serine and the other was trypstatin, the C-terminal half of the bikunin molecule. Three proteins containing covalently linked bikunin were also identified in pooled blood plasma. They were all dissociated into heavy and light chains by treatment with chondroitinase ABC or 50 mM NaOH, but not by heating at 100 degrees C in the presence of sodium dodecyl sulfate and dithiothreitol, N-terminal amino acid sequence analyses of the native chains and partially degraded fragments thereof revealed that these proteins are (i) human-type inter-alpha-trypsin inhibitor, consisting of heavy chains 1 and 2 and bikunin, (ii) bovine-type inter-alpha-trypsin inhibitor, consisting of heavy chains 2 and 3 and bikunin, and (iii) pre-alpha-trypsin inhibitor, consisting of heavy chain 3 and bikunin. Heterodimer of bikunin/heavy chain 1 or bikunin/heavy chain 2 was not detected. These results suggest that the composition, and hence function, of the inter-alpha-trypsin inhibitor family differs considerably from species to species.
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PMID:Inter-alpha-trypsin inhibitor and its related proteins in Syrian hamster urine and plasma. 886 57

Breast cancer is one of the leading causes of cancer-related deaths amongst women in the USA. The tumor microenvironment has been suggested to be an attractive therapeutic target for treatment of cancers. The glycosaminoglycan chondroitin sulfate, as part of the cellular microenvironment, consists of long linear chains of repeating disaccharide units, which are covalently attached to core proteins to form chondroitin sulfate-proteoglycans. In vitro studies have implicated chondroitin sulfate in various aspects of carcinogenesis, whereas the in vivo roles of chondroitin sulfate are less clear. Drastically elevated levels of chondroitin sulfate have been observed within the stromal compartment of many solid tumors, including human breast carcinomas, the significance of which is unknown. We examined the role of tumor-associated chondroitin sulfate in breast cancer progression. Enzymatic elimination of endogenous chondroitin sulfate by intra-tumor injections of chondroitinase ABC leads to the development of secondary tumors and increased lung metastases, while primary orthotopic tumor growth was not affected. These results establish a metastasis-inhibiting effect of primary breast tumor-associated chondroitin sulfate, which may open novel carbohydrate-based therapeutic strategies to combat breast cancer.
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PMID:Elimination of breast tumor-associated chondroitin sulfate promotes metastasis. 2218 49