Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A correlation between increased beta-1,6 branching of N-linked carbohydrates and the ability of a cell to metastasize or to form a tumor has been observed in several experimental models. Lec9 Chinese hamster ovary (CHO) mutants exhibit a drastic reduction in tumorigenicity in nude mice, and this phenotype directly correlates with their ability to attach an increased proportion of beta-1,6-branched carbohydrates to the G glycoprotein of vesicular stomatitis virus (J. Ripka, S. Shin, and P. Stanley, Mol. Cell. Biol. 6:1268-1275, 1986). In this paper we provide evidence that cellular carbohydrates from Lec9 cells also contain an increased proportion of beta-1,6-branched carbohydrates, although they do not possess significantly increased activity of the beta-1,6 branching enzyme (GlcNAc-transferase V). Biosynthetic labeling experiments show that a substantial degree of underglycosylation occurs in Lec9 cells and that this affects several classes of glycoproteins. Lec9 cells synthesize ca. 40-fold less Glc3Man9GlcNAc2-P-P-lipid and ca. 2-fold less Man5GlcNAc2-P-P-lipid than parental cells do. In addition, Lec9 cells possess ca. fivefold less protein-bound oligosaccharide intermediates, and one major species is resistant to release by endo-beta-N-acetylglucosaminidase H (endo H). Membranes of Lec9 cells exhibit normal mannosylphosphoryldolichol synthase, glucosylphosphoryldolichol synthase, and N-acetylglucosaminylphosphate transferase activities in the presence of exogenous dolichyl phosphate. However, in the absence of exogenous dolichyl phosphate, mannosylphosphoryldolichol synthase and glucosylphosphoryldolichol synthase activities are reduced in membranes of Lec9 cells, indicating that membranes of Lec9 cells are deficient in lipid phosphate. This was confirmed by analysis of lipids labeled by [3H]mevalonate, which showed that Lec9 cells have less lipid phosphate than parental CHO cells. Mechanisms by which a defect in the synthesis of dolichol-oligosaccharides might alter the degree of beta-1,6 branching in N-linked carbohydrates are discussed.
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PMID:Control of carbohydrate processing: increased beta-1,6 branching in N-linked carbohydrates of Lec9 CHO mutants appears to arise from a defect in oligosaccharide-dolichol biosynthesis. 272 6

Penetration of the extracellular matrix (ECM) by tumor cells, an event which occurs at various stages of the metastatic process, involves tumor cell glycosidase mediated hydrolysis of proteoglycans (PG). Recently, we observed that human ovarian carcinoma cell lines (HOCC) derived from primary tumors, peritoneal effusions, and distant metastases possess a varying ability to degrade radiolabeled PG of the ECM, while normal cells (human mesothelial cells or ovarian fibroblasts) fail to do so. To determine whether a quantitative relationship exists between glycosidase activity and degradation of ECM, both intracellular and extracellular glycosidase activities were measured for HOCC and normal cell lines. No relationship was found between intracellular glycosidase activities and the ability of cells to degrade ECM. However, a correlation was observed between extracellular or secretory glycosidase activities and HOCC mediated ECM degradation. In particular, a 5-8-fold increase, as compared to normal cells, was observed for HOCC extracellular beta-N-acetylglucosaminidase (EC 3.2.2.30) activity. The accumulation or secretion of this enzyme from HOCC into culture medium was found to be time dependent and not related to intracellular levels. Purified hexosaminidase derived from invasive HOCC was able to hydrolyze [3H]-glucosamine radiolabeled ECM (up to 30% radiolabel) and resulted in the cumulative release of free [3H]-N-acetylglucosamine. This enzyme mediated hydrolysis could be completely prevented with 2-acetamido-2-deoxy-1,5-D-gluconolactone, a competitive inhibitor (Ki 10(-6) M). Finally, HOCC mediated degradation of radiolabeled ECM was discerned to be dependent upon active hexosaminidase action, since tumor cell mediated degradation of ECM could be inhibited by up to 60% in the presence of this synthetic competitive inhibitor. In summary, these studies indicate a strong association between HOCC solubilization of glycoconjugates present in the ECM and extracellular levels of hexosaminidase.
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PMID:Role of glycosidases in human ovarian carcinoma cell mediated degradation of subendothelial extracellular matrix. 295 46

Blood group-related oligosaccharides have been isolated from a limited number of carcinomas. The carcinoma-associated oligosaccharides show chain elongation, for example due to repeating Gal 1,4 GlcNAc 1,3 sequences, or a higher degree of branching, which permit increased sialylation and fucosylation. Abnormal carbohydrate structures have been demonstrated on tumor cell membranes by immunological techniques, which suggests deletion of ABH, accumulation of 'crypt' antigens such as I and T antigens, and abnormal expression of Lewis antigens. Changes in carcinoma-associated oligosaccharides can result from altered biosynthetic processing in the Golgi apparatus or the occurrence of abnormal tumor glycosyltransferase isoenzymes. Structural alterations of oligosaccharides on the tumor cell membrane are related to the regulation of tumor growth, cell-cell interaction, cell differentiation, and metastasis. Glycoproteins secreted by tumor cells into the circulation evoke cellular and humoral immunity and cause immune suppression by binding to cytotoxic T lymphocytes and lymphocyte subsets. The relationship of oligosaccharide structures to biologic function awaits elucidation.
Cancer Metastasis Rev 1987
PMID:The structural relationship of blood group-related oligosaccharides in human carcinoma to biological function: a perspective. 332 32

In order to investigate possible differences in sugar binding activities of strongly versus weakly metastatic tumors, sugar-binding molecules (endogenous lectins) of murine tumor cells differing in metastatic capacity were analyzed by affinity chromatography on supports with immobilized sugars or glycoproteins and compared. After elution with specific sugar in the absence of Ca2+-ions, the proteins were separated by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis. In comparison to a weakly metastatic subline (Eb) spontaneous strongly metastatic variants (ESb) of a murine lymphoma contained additional sugar receptors for N-acetylglucosamine (Mr 30 kDa) and maltose (Mr 64 kDa, 62 kDa, 54 kDa and 32 kDa), and lacked one sugar receptor for myoinositol (Mr 85 kDa), N-acetylglucosamine (Mr 23 kDa) and maltose (Mr 22 kDa), respectively. The strongly metastatic variant ESb expressed the common beta-galactoside-specific lectin to a higher extent and receptors for myo-inositol, melibiose and mannan to a lower extent. In another model system derived from the murine mastocytoma cell line P 815 X 2A, biochemical analysis of the liver-metastasizing variant P 815 X 2B revealed additional characteristic N-acetylgalactosamine- and maltose-specific binding proteins. This variant had reduced amounts of receptors for beta-galactosides and fucose in comparison to the parental clone. In a third tumor system a similar qualitative difference was disclosed: a metastatic variant derived from spleen metastases displayed a sugar receptor profile with 5 additional beta-galactoside-binding proteins when compared to its parental clone 6-6#3 + F, which is a virally transformed fibroblast line. The results show that metastatic variants of 3 murine tumor models consisting of lymphomas, mastocytomas and sarcomas are characterized by qualitative and quantitative alterations in the profiles of sugar-binding proteins.
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PMID:Differential expression of endogenous sugar-binding proteins (lectins) in murine tumor model systems with metastatic capacity. 357 May 57

Recent studies have demonstrated that colonic carcinomas consist of heterogeneous populations of cells endowed with different abilities to metastasize. Increasing evidence suggests that cell surface carbohydrates may play an important role in cancer invasion and metastasis. Therefore the binding of five fluorescein isothiocyanate-conjugated lectins to cellular glycoconjugates was analyzed immunohistochemically in paraffin-embedded tissue sections obtained from 16 colorectal carcinomas and their 25 metastases. In positive cases peanut agglutinin (galactose beta 1----3N-acetylgalactosamine), Ulex europeus' agglutinin 1 (alpha-L-fucose), Griffonia simplicifolia agglutinin 1 (galactose), Vicia villosa agglutinin (N-acetylgalactosamine), and G. simplicifolia agglutinin 2 (N-acetylglucosamine) stained apical cell membranes in carcinomatous glands and intraluminal secretions. Nine of 16 primary colorectal carcinomas showed intratumoral heterogeneous cell populations with regard to the lectin binding which resulted in areas of fluorescence-positive and fluorescence-negative carcinomatous glands. Only one liver metastasis showed this intralesional heterogeneity in lectin binding. Nineteen of 25 metastatic tumors produced cellular glycoconjugates which differed in their lectin binding profiles from those made by the majority of the cells in the respective primary colorectal carcinomas. The findings of the present work suggest that many primary colorectal carcinomas consist of phenotypically distinct subpopulations of carcinomatous cells. Most metastatic tumors appeared to result from a selective emergence of carcinoma cells producing glycoconjugates which differed in their lectin-binding profiles from those in their respective primary colorectal carcinomas.
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PMID:Differences in lectin reactivities of cellular glycoconjugates between primary human colorectal carcinomas and their metastases. 373 Nov 14

The levels of UDP-galactose: N-acetylglucosamine(beta 1-4)galactosyltransferase activity (GalT-4) were determined in the sera, in solid tumors, and in corresponding cell cultures of rats bearing two lines of prostate adenocarcinomas (PA-2 and PA-3), and in the sera of rats bearing other transplanted and autochthonous adenocarcinomas. Sera and tissues from normal (tumor-free) rats were used as controls. Prostate adenocarcinoma cell cultures had five times greater levels of enzyme activity than did tumor cell infiltrated lymph nodes from animals bearing the prostate adenocarcinomas. The levels of activity in the cells of both prostate tumor lines were equivalent, even though they metastasize through different routes. Serum levels of galactosyltransferase activity were detected in the blood, and in rats bearing a mammary adenocarcinoma with extensive necrosis of the tumor mass (tumor mass greater than 22.0 g/200 g body weight). The increase was three times the control value. The sera of L-W rats bearing prostate tumors (PA-2 and PA-3) were inactive with the GalNAc-containing acceptor, Gm2 (GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta 1-4Glc-Cer) but active with either free GlcNAc (Km = 0.25 mM) or LcOse3Cer (GlcNAc beta 1-3 Gal beta 1-4Glc--Cer; GlcNAc--R).
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PMID:Increased activity of a beta-galactosyltransferase in tissues of rats bearing prostate and mammary adenocarcinomas. 680 31

Blood group antigen-related oligosaccharides have been implicated in growth regulation, cell mobility control and adhesion; we are therefore interested in the localization of receptors for these oligosaccharides in tumour cells. Labelled neoglycoconjugates that carry synthetic sugar structures are suitable tools to determine: whether such binding sites are present in human lung cancer; whether structural alterations of the glycoligand part will affect extent of binding; and whether cell type-associated alterations can be detected. Sections from 121 cases of lung cancer, representing small cell and non-small cell lung carcinoma, mesothelioma and metastases from extrapulmonary primary carcinomas were used to study the binding of nine synthetic AH- and Le-related oligosaccharides. Probes with fucose-alpha 1-3/4-N-acetylglucosamine-beta 1-R, an A-like disaccharide and 3'-sulfated galactose as ligand appear to bind less well to small cell than to non-small cell lung cancer cases, whereas Lec-disaccharide distinguishes mesothelioma from metastatic carcinoma. The latter ligand, A-like disaccharide and H (type III)-like trisaccharide exhibit evident cell type-associated differences in extent of binding. Thus, tailor-made neoglycoconjugates constitute a promising class of histopathological tools that warrants further study.
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PMID:Cell type-dependent alterations of binding of synthetic blood group antigen-related oligosaccharides in lung cancer. 787 30

Human chorionic gonadotropin (hCG) is a glycoprotein of which sugar chains are considered to show structural changes with malignancy. To study the sugar chain heterogeneity of urinary hCG in patients with gynecological disease, we employed serial lectin affinity chromatography (LAC) using concanavalin A (Con A) and phytohemagglutinin-E (PHA-E) which can separate N-glycoside-linked sugar chains, and Jacalin lectin which is specific for O-glycoside-linked sugar chains. The proportion of hCG which did not bind to Con A was clearly higher in patients with cervical cancer than in healthy pregnant women. The complex-type sugar chains bearing bisecting (beta 1-4) N-acetylglucosamine which bound to PHA-E increased in the early stage of cervical cancer, and tri- and tetra-antennary complex type sugar chains also increased in the advanced stages. In addition, the Jacalin-bound hCG increased significantly along with the stage of the cancer, especially in advanced cervical cancer with distant metastases. Taken together, these results show that alteration in sugar chain structures of hCG reflect the advanced stage of cervical cancer.
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PMID:Sugar chain heterogeneity of human urinary chorionic gonadotropin determined by serial lectin affinity chromatography: difference between benign and malignant disease. 793 72

Combined analysis of the binding properties of inflammatory and tumor cells in pleural effusion, and tumor imprints for various carrier-immobilized types of ligands and lectins, and of a biochemical feature of the effusions is performed to extend the characterization of these cells and their activity. In detail, the binding of Viscum album agglutinin (VAA), Urtica dioica agglutinin (UDA), and of carrier-immobilized N-acetyl-D-glucosamine (GlcNAc), lysoganglioside GM1, estradiol, progesterone, testosterone, and hydrocortisone to native specimens consisting of 46 tumor imprints from surgically treated patients with lung cancer and 74 smears of pleural effusion (PE) cells from cancer or non-cancer patients was studied using fluorescence microscopy with Texas red-labeled streptavidin. Among the tested ligands, VAA was found to provide the most effective staining of cells (60-78.1% of positive cases). When compared with inflammatory cells from PE, cancer cells were seen to bind more frequently only two ligands, namely UDA and estradiol. Significant (P < 0.001) difference between patients with bronchial carcinoma and non-cancer patients were found, when the content of NO2-/NO3- in PE fluids was measured. Whereas the level of NO2-/NO3- in PE of non-cancer patients was 12.6 +/- 10.7 microM (n = 12), it was 37.7 +/- 19.4 microM (n = 14) in cancer patients without pleural metastases and 37.5 +/- 16.0 microM (n = 26) in patients with pleural metastases. The level of NO2-/NO3- in PE appeared to correlate with extent of staining with GM1 and GlcNAc: in non-cancer patient groups it was significantly higher (P = 0.032) for negative subjects than those binding the ligand GlcNAc, whereas in the patient group with adenocarcinoma it was significantly lower (P = 0.032) for patients without binding capacities for GlcNAc and GM1. The results obtained suggest that the combined analysis of increased levels of NO2-/NO3- in PE and of glycohistochemical properties of cancer and inflammatory cells may be useful in exploring the interrelationship of functionally important cellular characteristics.
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PMID:Binding capacities of two immunomodulatory lectins, carrier-immobilized glycoligands and steroid hormones in lung cancer and the concentration of nitrite/nitrate in pleural effusions. 869 22

The expression of -GlcNAc beta 1-6Man-(beta 1-6) branched oligosaccharides in carcinoma cells has been considered to influence their metastatic potentials. In the present paper, the lectin histochemistry of oral squamous cell carcinomas obtained in biopsy from 34 patients with Phaseolus vulgaris leukoagglutinin (L-PHA), which potentially binds to N-glycosidic carbohydrates with beta 1-6 linked lactosamin antennae, was studied in order to analyze the relationship between their staining patterns and metastases. The L-PHA-binding oligosaccharides of the carcinomas were expressed on the cell surface in the following patterns: (i) all cells were positive for the staining ('positive'); (ii) some cells were positive but the rest of the carcinoma cells were negative ('weakly positive'); and (iii) all were negative ('negative'). Statistical analysis revealed that the incidence of the metastasis to regional lymph nodes in the 'positive' cases was significantly higher than that in the 'negative' cases. Moreover, the number of the CD14 positive cells including macrophages in the stroma adjacent to the carcinomas in the 'positive' cases was less than that in the 'negative' or 'weakly positive' cases. The expression of L-PHA-binding oligosaccharides in oral squamous cell carcinoma may be responsible for their metastatic potential to regional lymph nodes, possibly including their ability to escape macrophage recognition.
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PMID:Expression of Phaseolus vulgaris leukoagglutinin-binding oligosaccharides in oral squamous cell carcinoma: possible association with the metastatic potential. 890 72


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