Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycoprotein synthesis and secretion were measured in short-term organ culture of normal and neoplastic colonic mucosa from 11 patients undergoing colectomy for colon cancer. Mucosal explants were incubated for up to 24 hr with [3H]glucosamine, which was incorporated into both explant and secreted glycoproteins. Structural and functional viability was documented by morphological studies that showed excellent preservation of architectural detail and biochemical studies that documented a steady increase in glycoprotein synthesis during 24-hr incubation. The major difference between normal and neoplastic mucosa was a 35% decrease (p less than 0.02) in the incorporation of [3H]glucosamine into tumor explants, as compared to the amount incorporated into normal explants from the same patient. The rate of secretion of radiolabeled glycoproteins into the medium did not differ significantly. Separation of explants into particulate and cytosol fractions showed that the overall decreases in glycoprotein synthesis in tumor explants was primarily due to a marked reduction in particulate glycoprotein synthesis in the cancer tissue.
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PMID:Glycoprotein synthesis and secretion in human colon cancers and normal colonic mucosa. 67 85

Many cancer-associated antigens are present on mucin glycoproteins. These include peripheral antigens such as sialyl Lea and sialyl Lex and core region carbohydrate antigens such as T, Tn, and Sialyl Tn. We have recently described an inhibitor of mucin glycosylation, benzyl-alpha-GalNAc. The purpose of this study was to determine its effect on expression of mucin carbohydrate antigens. HM7 colon cancer cells were treated for 2 days in culture with 2 mM benzyl-alpha-GalNAc. This treatment did not affect viability or doubling time, but inhibited synthesis of [3H]glucosamine-labeled mucins. There was also secretion of benzyl-oligosaccharides and a decrease in the proportion of long oligosaccharides on 3H-labeled mucins. Mucins were purified from spent media by gel filtration and assayed for binding of monoclonal antibodies and lectins. Mucins from benzyl-alpha-GalNAc-treated cells had increased binding of peanut agglutinin (specific for T antigen, Gal beta 3GalNAc) and Vicia villosa agglutinin B4 (specific for Tn antigen, GalNAc alpha-Thr/Ser), but decreased binding of monoclonal antibodies 19-9, SNH3, and 91.9H (specific for sialyl Lea, sialyl Lex, and sulfomucin, respectively). Treatment of the cells with benzyl-alpha-GalNAc also decreased their binding to E-selectin (ELAM-1), which recognizes sialyl Lea and sialyl Lex. Thus, benzyl-alpha-GalNAc treatment, which decreases the level of peripheral carbohydrate carbohydrate antigens on mucins with accumulation of core region antigens, may be useful in modifying the immunological and biological properties of colon cancer cells.
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PMID:Effect of benzyl-alpha-GalNAc, an inhibitor of mucin glycosylation, on cancer-associated antigens in human colon cancer cells. 128 81

The in vitro effect of butyrate on expression of differentiation markers in colonic epithelial cells was assessed in the colon cancer cell line, LIM1215 and in epithelial cells isolated from a surgically resected histologically normal colon. Markers used to assess cell differentiation were: net glycoprotein synthesis ([3H]-glucosamine uptake) expressed relative to net protein synthesis ([14C]-leucine uptake), and the expression of the brush border glycoproteins (alkaline phosphatase and carcino-embryonic antigen) in cell homogenates calculated relative to cellular protein content. In response to 24 h exposure to 1 mmol/L butyrate, all markers significantly increased in LIM1215 cells whereas they all significantly decreased in isolated colonic epithelial cells under identical culture conditions. Similar effects were seen at butyrate concentrations of up to 4 mmol/L. Butyrate suppressed proliferation of LIM1215 cells but had no consistent effect on [3H]-thymidine uptake by, or DNA content of, normal epithelial cells. Additional experiments found no evidence of a toxic effect of butyrate at those concentrations nor of an alteration of cell responsiveness to butyrate due to the isolation process itself. In contrast to its differentiative effect on neoplastic cells, butyrate reduces the expression of phenotypic markers of differentiation in vitro in colonic epithelial cells from non-neoplastic mucosa.
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PMID:Contrasting effects of butyrate on the expression of phenotypic markers of differentiation in neoplastic and non-neoplastic colonic epithelial cells in vitro. 157 99

The synthesis and secretion of mucin-like high-molecular glycoprotein was studied in 2 human colon cancer cell lines that spontaneously differentiate in culture (Caco-2 and T84) and in 2 cell lines that do not spontaneously differentiate (LS174T and HT29). Mucin, quantitated by 3H-glucosamine labelling and chromatography on Sepharose CL-4B was found to be produced by all 4 cell lines. The mucinous nature of the labelled high-molecular glycoprotein was verified by enzymatic degradation treatments (heparinase, hyaluronidase, chondroitinase ABC, and N-glycanase), alkaline-borohydride treatment, inhibition of labelling by the glycosylation inhibitor benzyl-alpha-GalNAc, and by CsCl-density-gradient centrifugation. In all 4 cell lines, an inverse correlation of mucin synthesis with cell density was demonstrated. In Caco-2 cells, the spontaneous post-confluent enterocytic differentiation with increased brush-border enzyme expression was associated with a decrease in mucin synthesis and in the activities of polypeptidyl GalNAc transferase and beta 1,3-galactosyltransferase activity. Using cDNA probes for 2 distinct human intestinal mucins (MUC2 and MUC3), we found that all 4 colon cancer cell lines expressed mucin message, but the types of mucin mRNA expressed differed. These data indicate that mucin-like glycoproteins can be synthesized by cell lines derived from non-mucinous colon cancer, whether or not they undergo spontaneous differentiation in culture. These cell lines may serve as in vitro models for studying apomucin heterogeneity and control of mucin gene expression.
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PMID:Mucin synthesis and secretion in relation to spontaneous differentiation of colon cancer cells in vitro. 172 5

A lectin reactivity specific to human bowel carcinoma is reported. Twenty-six cases of carcinoma of the large intestine were examined. Normal as well as transitional mucosa and carcinoma tissues were removed from surgical specimens, and paraffin sections were stained with a battery of histochemical methods to characterize glycoconjugates, including high iron diamine-Alcian blue pH 2.5, modified PAS reaction to detect various sialic acids, paradoxical concanavalin A (Con A) staining, and stainings with 10 species of lectins labeled with horseradish peroxidase (HRP). Among the techniques employed, only Griffonia simplicifolia agglutinin-II (GS-II, specific to glucosamine)-HRP staining revealed highly selective affinity to the carcinoma tissues; the apical surface of the carcinoma cells stained most intensely. GS-II reactivity of the cells persisted after prior periodate oxidation, but was significantly enhanced by neuraminidase digestion. Comparison with two other lectin stainings with the same sugar specificity, viz. paradoxical concanavalin A staining and wheat germ agglutinin (WGA)-HRP staining, showed that the GS-II reactive sites lacked class III Con A reactivity but were possibly included in WGA reactive sites. The GS-II-HRP staining should be helpful in the identification of carcinoma tissue and for analysis of carcinoma-associated antigens.
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PMID:Large bowel carcinoma-specific antigens detected by the lectin, Griffonia simplicifolia agglutinin-II. 241 1

Specific inhibitors of the glycosylation of O-glycosidically linked glycoproteins have not previously been described. When tested for their effects on mucin glycosylation in a mucin-producing colon cancer cell line, LS174T, benzyl-, phenyl-, and p-nitrophenyl-N-acetyl-alpha-galactosaminide inhibited the formation of fully glycosylated mucin in a dose-dependent manner. Free aryl-oligosaccharides were found in the medium of treated cells labeled with [3H]glucosamine, [3H]galactose, [3H]fucose, [3H]mannosamine, or phenyl-alpha-[6-3H] N-acetylgalactosamine. UDP-Gal:GalNAc-beta 1,3-galactosyltransferase was inhibited by aryl-N-acetyl-alpha-galactosaminides but not by a number of other aryl-glycosides. Treatment with these inhibitors also causes reversible morphologic changes including formation of intercellular cysts. Aryl-N-acetyl-alpha-galactosaminides can be useful for the structural and functional studies of mucin macromolecules and other O-linked glycoproteins.
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PMID:Inhibition of mucin glycosylation by aryl-N-acetyl-alpha-galactosaminides in human colon cancer cells. 250 74

Colon cancer cells in culture synthesize and secrete mucin glycoproteins, which carry a number of cancer-associated antigens. However, the structures and mechanisms of biosynthetic processing are not well understood. Mucins synthesized and secreted by LS174T human colon cancer cells were compared to those in LS174T xenografts in athymic mice. Mucins radiolabeled with glucosamine or sulfate were purified by gel filtration and cesium chloride density gradient centrifugation. The mucins were of high molecular weight and were resistant to chondroitinase ABC, hyaluronidase and HNO2 treatment. They were, however, susceptible to pronase digestion and mild alkaline treatment. Using radiochemical precursors, the cellular mucin was shown to contain fucose, galactose, N-acetylgalactosamine, N-acetylglucosamine, N-acetylneuraminic acid, and sulfate. Oligosaccharides released by beta-elimination had N-acetylgalactosaminitol as the reduced amino sugar and also unreduced galactosamine, indicating that there is N-acetyl-galactosamine O-glycosidically attached to protein core and also peripheral N-acetyl-galactosamine not directly linked to protein. DEAE-cellulose chromatography of mucins showed two major peaks with both intracellular and secreted mucins, but xenograft mucins also had more acidic components. Sulfate-labeled mucins were shifted to less acidic peaks by neuraminidase digestion, which indicates that the same mucin molecules are both sialylated and sulfated. We conclude that the intracellular mucins of cultured colon cancer cells, those secreted into the medium, and those in nude mouse xenografts are chemically similar, but differ in sialic acid and sulfate content. This experimental model system, LS174T cells maintained in culture and as nude mouse xenografts, may be useful for further biosynthetic and structural studies of colon cancer mucin.
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PMID:Comparison of metabolically labeled mucins of LS174T human colon cancer cells in tissue culture and xenograft. 273 49

A high molecular weight, mucous glycoprotein (MG) from the pleural fluid of lung adenocarcinoma was purified by the DEAE-cellulose, gel-filtration and wheat germ agglutinin affinity chromatography. Protein portion of the molecule was composed of amino acids rich in serine, threonine and proline, but methionine and tyrosine concentrations were relatively low. About 65% of the weight, was composed of galactose, galactosamine, glucosamine, fucose and sialic acid. The gel-filtration pattern on Sepharose 4B revealed Mr greater than 10(6) Da. The SDS-PAGE pattern revealed a main band at the position of the Mr about 350 kDa under the reducing condition. Rabbit antibody against this molecule recognized mainly the peptide portion, and the radioimmunoassay (RIA) using the double antibody method was developed by this antibody. Serum MG level was low in healthy subjects and in benign diseases (0.8 +/- 0.7 U/ml; mean +/- SD and 1.1 +/- 2.3 U/ml, respectively). Thus, 3 U/ml was used as the cut-off value. The mean of serum MG levels and positive rates in malignant diseases were significantly high; 4.4 U/ml and 32.3% in lung cancer, 20.1 U/ml and 77.5% in pancreas cancer 11.6 U/ml and 64.3% in gastric cancer, 12.9 U/ml and 57.1% in hepatoma, 12.3 U/ml and 77.8 in colon cancer. Other malignancies such as ovarial and uterus cancer showed also high levels. Elevated values in these malignancies were observed frequently in patients with metastasis. On the other hand, the false positive cases were found in 10% of benign diseases. Determination of MG seems to be useful for the detection of several kinds of malignancies, but it is not adequately sensitive as a screening method for early cancer detection.
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PMID:Clinical significance of mucin-like high molecular weight glycoprotein originated from lung cancer as tumor marker. 274 68

Mucin from xenografts of LS174T human colon cancer cells was treated with anhydrous HF for 1 h at 0 degree C to give a product (HFA) with over 80% of the glucosamine and hexose removed, but retaining some galactosamine, and for 3 h at room temperature to give a product (HFB) devoid of carbohydrate. Rabbit antibodies against HFA bound to HFA much more than to HFB, and bound to native mucin to an intermediate extent. Antibodies to HFB bound to HFB more than to HFA, and did not bind to native mucin. Both HFA and native mucin bound a number of lectins, but HFB did not. By SDS/polyacrylamide-gel electrophoresis and size-exclusion h.p.l.c., native mucin and HFA are of apparent molecular mass greater than 400 kDa, whereas HFB is heterogeneous and of low molecular mass. On Western blots, antibody to HFA detected both high-molecular-mass mucin and a 90 kDa protein in homogenates of LS174T cells. Antibody to HFB detected a major 70 kDa band as well as higher-molecular-mass species. In tissue sections of normal colon and colon cancers, antibody to HFA showed both cytoplasmic and extracellular staining, whereas antibody to HFB generally stained only cytoplasmic antigens. These results indicate that anti-HFB antibody is specific for apo-mucin, whereas anti-HFA antibody is specific for GalNAc-apo-mucin.
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PMID:Deglycosylation of mucin from LS174T colon cancer cells by hydrogen fluoride treatment. 277 37

The structure of colonic mucin, which is thought to be important in several diseases, including ulcerative colitis and colon cancer, is poorly understood. Mucin was isolated from nude mouse xenografts of the LS174T colonic adenocarcinoma cell line by gel filtration and CsCl density gradient centrifugation. The isolated mucin had a high content of threonine, serine, and proline, with 28% of the total amino acids O-glycosylated. The carbohydrates present were fucose, sialic acid, galactose, N-acetyl-glucosamine, and N-acetyl-galactosamine in the ratio of 0.4:1.5:1.0:0.9:1.4. Rabbit antibodies were prepared that recognized primarily protein-dependent determinants. By DEAE-cellulose chromatography, the purified mucin was found to be heterogeneous, with three major components that had small differences in carbohydrate composition. LS174T was antigenically and chromatographically similar to mucins in colon cancer tissue specimens and in nonmalignant colonic mucosae.
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PMID:Isolation and characterization of colon cancer mucin from xenografts of LS174T cells. 318 78


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