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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BUB/BnJ mice were previously identified as having exceptionally potent complement activity, relative to common mouse strains, in the lysis of antibody-coated human tumor cells. We describe herein our investigation into the molecular and genetic basis for this difference between mouse strains, and also our results with wild mice and mouse strains recently derived from the wild, to determine whether low complement levels are characteristic of wild mice. BUB complement was compared with complement from BALB/c and C57BL/6 mice. BUB mice had higher levels of most individual classical pathway components, except for C1, than the other two strains, but the difference was generally only 2-3-fold, so insufficient to fully explain the difference observed with tumor target cells. CH50 titers on antibody-coated sheep erythrocytes also demonstrated only a 2-4-fold difference. However, CH50 titers on antibody-coated human erythrocyte target cells demonstrated a difference similar in magnitude to that seen with human tumor targets. These results suggest that the difference between mouse strains depends partly on the use of human, rather than sheep, target cells. In an assay for alternative complement pathway activity using neuraminidase-treated human erythrocytes as targets, complements of BALB/c and BUB mice were similar in activity, suggesting that the difference between mouse strains is manifested in the early steps of complement activation. Analysis of F1 and backcross mice suggested that the difference in complement level between BUB and BALB/c or C57BL/6 mice is controlled by semi-dominant genes, and cannot be attributed to a single gene. Wild mice and mice recently derived from the wild generally had low complement levels, similar to most laboratory mice. However, three strains of aboriginal mice, including Mus hortulanus (spicilegus) and Mus spretus, had complement levels higher than that of BUB mice, and as high as sera from the rabbit or rat, which are the most potent known complement sources for the lysis of human tumor cells. In comparison with BUB mouse sera, M. hortulanus sera had at least four-fold higher levels of C3, C6, C8 and C9, and some or all of these differences may explain its higher total complement activity. In the lysis of antibody-coated human erythrocytes, M. hortulanus serum was more potent than any other complement source tested, including sera of the guinea pig, rat, rabbit or human. These strains may be useful in investigating the role of complement in various pathological processes, and in investigating the genetic regulation of the complement system.
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PMID:Analysis of high complement levels in Mus hortulanus and BUB mice. 140 42

The peanut agglutinin (PNA)-binding site is protein-bound Gal beta 1-->3GalNAc, and is a tumor-associated carbohydrate marker expressed in many human carcinomas. PNA-binding glycoproteins isolated from KATO-III human gastric carcinoma cells were deglycosylated by trifluoromethanesulfonic acid, and rabbit antibodies against the core proteins were used to screen a lambda gt11 expression library constructed from these cells. Two different core proteins were identified by this approach. One was polymorphic epithelial mucin (PEM), initially found in breast carcinomas. PEM mRNA was expressed in normal tissues of the stomach, colon, and lung, but not in the small intestine, thyroid, and spleen. High levels of PEM mRNA were detected in some nude mouse-transplanted carcinomas, i.e. colorectal, pancreatic, stomach, and lung carcinomas. The other core protein was a novel one called MGC-24, which has a molecular mass of 24 kDa, is rich in hydroxyl amino acids and cysteine, and lacks repeating motifs. The mature MGC-24 glycoprotein behaved as a high-molecular-mass one upon SDS-polyacrylamide gel electrophoresis even after neuraminidase treatment. Treatment with endo-alpha-N-acetylgalactosaminidase in the absence of neuraminidase significantly changed the staining pattern by anti-MGC-24, confirming that MGC-24 carried PNA-binding sites. MGC-24 mRNA was intensely expressed in normal tissues of the colon, small intestine and thyroid, and in some nude mouse-transplanted colorectal and pancreatic adenocarcinomas.
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PMID:A novel core protein as well as polymorphic epithelial mucin carry peanut agglutinin binding sites in human gastric carcinoma cells: sequence analysis and examination of gene expression. 147 19

Initial adhesion of B16 melanoma variants to non-activated endothelial cells is mediated through specific interaction between GM3 (NeuAc alpha 2----3Gal beta 1----4Glc beta 1----Cer) expressed on melanoma cells and lactosylceramide (LacCer, Gal beta 1----4Glc beta 1----Cer) expressed on endothelial cells. This adhesion is predominant over integrin- or lectin-mediated adhesion in a dynamic flow experimental system employing a parallel plate laminar flow chamber (Lawrence, M. B., Smith, C. W., Eskin, S. G., and McIntire, L. V. (1990) Blood 75, 227-237). In this system, a tumor cell suspension flows over a glass plate coated with glycosphingolipid, lectin, or fibronectin, and adhesion is recorded on videotape. These conditions were designed to mimic the microvascular environment in which tumor metastatic deposition takes place. In contrast, lectin- and fibronectin-based mechanisms are predominant in previously used static adhesion systems. Under static conditions, the relative degree of adhesion of the four B16 variants to endothelial cells or to LacCer-coated plates was the same as their relative degree of GM3 expression (i.e. BL6 approximately F10 greater than F1 greater than WA4), and adhesion was inhibited in the presence of methyl-beta-lactoside, or liposomes containing LacCer or GM3. Adhesion was also inhibited by pretreatment of B16 cells with anti-GM3 antibody DH2 or sialidase and by pretreatment of endothelial cells with anti-LacCer antibody T5A7. Under dynamic flow conditions, WA4 cells did not adhere to mouse endothelial cells at high shear stress (greater than 2.5 dynes/cm2) but did adhere at lower shear stress. In contrast, BL6 and F10 cells adhered strongly at both low and high shear stress. BL6 cell adhesion to endothelial cells at both low and high shear stress was inhibited in the presence of antibody DH2, ethyl-beta-lactoside, or lactose, as well as by pretreatment of BL6 cells with sialidase. Thus, some clear differences, as well as similarities, in cell adhesion under static versus dynamic conditions are demonstrated. These findings suggest that melanoma cell adhesion to endothelial cells, based on GM3/LacCer interaction, initiates metastatic deposition, which may trigger a series of "cascade" reactions leading to activation of endothelial cells and expression of Ig family or selectin receptors, thereby promoting adhesion and migration of tumor cells.
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PMID:Cell adhesion in a dynamic flow system as compared to static system. Glycosphingolipid-glycosphingolipid interaction in the dynamic system predominates over lectin- or integrin-based mechanisms in adhesion of B16 melanoma cells to non-activated endothelial cells. 151 64

Colorectal tumor tissue directly obtained from the surgeon was dissociated by enzymatical and mechanical disruption into a suspension of single cells of high viability. Homotypic aggregation, sialidase-accessible sialic acid and total fucose content of tumor cells were determined. Aggregation of cells from mucinous tumors was found to be significantly lower than of cells from nonmucinous tissue. The median value of surface-bound sialic acid was lower in strongly aggregating cells compared to nonaggregating cells. Cells from metastasizing tumors showed slightly lower aggregation, but on an average carried more surface-bound sialic acid and were significantly higher fucosylated than cells from nonmetastasizing tumors.
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PMID:Homotypic aggregation and terminal glycosylation of cells from dissociated human colorectal tumor tissue. 154 97

SCK-29 is a tumor cell line derived from human gastric adenocarcinoma with the feature of producing lung metastases when xenografted in nude mice. Monoclonal antibodies were produced against SCK-29 tumor cells or their glycoproteins prepared by affinity chromatography on a lectin-agarose column. Five antigens defined by the monoclonal antibodies MG-1 to MG-5 were expressed in a large number of gastric or colonic adenocarcinomas. Among the antigens, MG-1 and MG-3 proved to be tumor-associated, since they were detected only occasionally in normal tissues. MG-5 antigen was often detected in normal gastric mucosa but not in other tissues. The degree of expression of MG-1. MG-3 and MG-5 antigens differed considerably in metastatic lesions. In metastatic liver lesions of gastric adenocarcinoma, expression of these MG antigens was less marked than in primary tumors. MG-1 and MG-3 antigens were abolished by neuraminidase digestion and periodate oxidation. MG-5 antigen was likely to be a protein antigen, since it was resistant to neuraminidase digestion and to periodate oxidation but was sensitive to protease digestion.
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PMID:Monoclonal antibodies against a human gastric cancer cell line with lung metastatic potential in nude mice define antigens with different expression between the primary and metastatic liver lesions. 154 89

Many previous studies have implicated cell surface saccharides, and sialylglycoconjugates in particular, as important mediators of tumor cell metastasis. In this report, we have used three different specific sialidases and a highly sensitive high-performance liquid chromatographic sialic acid assay to probe the cell surfaces of several murine adrenal carcinoma variants. In contrast to several earlier studies on other metastatic variants, we find no significant differences in the overall levels of cell surface or total cellular sialic acid among three Y1 murine adrenal carcinoma variants with widely different metastatic phenotypes. However, using highly purified, linkage-specific sialyltransferases, in conjunction with V. cholerae sialidase, to probe the cell surface saccharide topography of specific penultimate oligosaccharides, we do find striking differences in oligosaccharide structures underlying the sialic acid moieties. Two tumorigenic and metastatic variants (F2 and F4) contain about 6-fold more penultimate Gal beta 1----4GlcNAc sialylation sites than a related tumorigenic but nonmetastatic variant (HSR) when CMP-[3H]-N-acetylneuraminic acid and the Gal beta 1----4GlcNAc alpha 2,6 sialyltransferase are used to probe the adrenal carcinoma cell surfaces. The metastatic variants also are found to contain 4- to 4.5-fold more Gal beta 1----3GalNAc sialylation sites than the nonmetastatic variant when the Gal beta 1----3GalNAc alpha 2,3 sialyltransferase is used as a cell surface probe. Earlier work, which used the same sialyltransferase probes on sialidase-treated murine melanoma variants (A. Passaniti and G. W. Hart, J. Biol. Chem., 263: 7591-7603, 1988), also showed similar quantitative differences in penultimate structures between metastatic variants. However, in contrast to the adrenal carcinoma cells, the highly metastatic melanoma cells have severalfold lower levels of sialylatable penultimate Gal beta 1----4GlcNAc and Gal beta 1----3GalNAc saccharides compared to their nonmetastatic counterparts. Thus, while the precise structural alterations or surface accessibilities of penultimate saccharides appear to be cell type dependent, these results suggest that pronounced changes in penultimate cell surface sialo-oligosaccharide moieties occur during progression to a malignant phenotype in two widely different tumor systems. These types of alterations in the underlying penultimate oligosaccharide structures of cell surface sialoglycoconjugates may be a common feature of highly metastatic cells arising from very different tumor cell types.
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PMID:Adrenal carcinoma tumor progression and penultimate cell surface oligosaccharides. 155 26

Total saliva and secretions from parotid and submandibular glands of patients with carcinomas in the oral cavity, oropharynx or larynx and a control group of healthy individuals were analyzed for concentrations of glycosidically bound sugars and free N-acetylneuraminic acid as well as for sialidase activity. When compared to the data obtained for normal donors, the relative amounts of the individual monosaccharides fucose, galactose, mannose, N-acetylgalactosamine, and N-acetylglucosamine as components of glycoconjugates showed variable differences to the group of tumor patients depending on the type of secretion and the location of the tumor. The percentage of glycosidically linked N-acetylneuraminic acid, however, was always higher for the healthy donors. A significant difference was found in the amount of free sialic acid, with the exception of submandibular gland secretion from a patient with an oropharyngeal carcinoma, and sialidase activity which were increased for tumor patients, independent of the type of secretion and the location of the tumor. From these results it is concluded that free sialic acid and sialidase activity may be considered as markers for carcinomas in the upper aerodigestive tract.
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PMID:Analysis of carbohydrate composition and sialidase activity in oral secretions of patients with tumors in the upper aerodigestive tract. 156 17

The production of TNF-alpha and TNF-beta by human B-cell lines was studied at both the molecular and biological levels. The 24 B-cell lines studied included EBV+ cell lines (n = 13), EBV- cell lines (n = 8), and AIDS-associated B-cell lines (AABCL) (n = 3) which are EBV+/HIV-. Whereas radioimmunoprecipitation using TNF-alpha antisera detected 17-kDa TNF-alpha as expected, similar studies with anti-TNF-beta antisera revealed TNF-beta microheterogeneity. In the AABCL three bands with approximate MW of 26, 24, and 22 kDa were detected under reducing conditions, and in the non-AABCL, two bands only with 26 and 22 kDa were observed. To determine whether the size heterogeneity of TNF-beta is due to glycosylation, TNF-beta deglycosylation studies were done in two AABCL (PA682BM-2, PA682PE-1) and one non-AABCL (IM-1178). As control, the normal lymphoblastoid B-cell line RPMI-1788, which is known to secrete TNF-beta with MW 25 and 20 kDa, has been used. Deglycosylation studies using N-glycanase + neuraminidase + O-glycanase reduced the various bands in all cell lines to one band with 18.6 kDa, which is compatible with the TNF-beta backbone. In attempt to determine whether the differential glycosylation of TNF has any functional significance, all 24 cell lines were studied for TNF secretion and for TNF neutralization by monoclonal antibodies and polyclonal antibodies to TNF-alpha and TNF-beta. Constitutive secretion of TNF-alpha and TNF-beta has been detected only in the three AABCL. Following activation with the tumor promoter teleocidin, the secretion of both TNFs has been triggered in 2/8 EBV- cell lines and in 8/13 EBV+ non-AABCL. Using rabbit polyclonal antibodies to human TNF-alpha and to human TNF-beta, only little if any neutralization of these TNFs has been shown. Our data suggest that the differences in glycosylation of B-cell-derived TNFs may account for the incomplete neutralization, and may influence the cytotoxic biological activity of this lymphokine.
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PMID:Human B-cell TNF-beta microheterogeneity. 157 46

Cultured murine bone marrow-derived macrophage (BMM phi) can be induced to secrete tumoricidal activity in vitro when activated with recombinant IFN-gamma and bacterial lipopolysaccharide (LPS). We have analyzed this activity for tumor specificity, relationship to tumor necrosis factor-alpha (TNF-alpha), serine proteases, and reactive nitrogen intermediates, and partially purified this activity by high pressure liquid chromatography. Cytolytic activity was recovered in conditioned culture supernatants of serum-free cultivated BMM phi treated with a combination of IFN-gamma and LPS but was not inducible by either stimulant alone. It selectively affected tumor cells of murine as well as human origin irrespective of sensitivity towards recombinant murine TNF-alpha (r-muTNF-alpha), but did not significantly affect non-tumorigenic cells of either species. It was inactivated by 56 degrees C, trypsin, and neuraminidase treatment, but could not be inhibited by neutralizing antibodies against r-muTNF-alpha or serine protease inhibitors. Tumoricidal activity was purified approximately 10-fold by gel filtration and eluted as a major peak with a Mr of 170 kDa, containing a single predominant protein band of approximately 170 kDa on SDS-PAGE analysis, which is shown to be a disulfide linked glycoprotein heterodimer of 110 and 58 kDa subunits (gp170). Expression of this glycoprotein was strongly dependent on activation of BMM phi by a combination of IFN-gamma and LPS but was only marginally induced by either stimulant alone. Furthermore, the level of gp170 expression was quantitatively correlated with the tumoricidal activity of BMM phi culture supernatants, whereas no such correlation was found with respect to the amount of secreted TNF-alpha or reactive nitrogen intermediates. These data demonstrate that activated murine BMM phi secrete a tumoricidal activity, which is not related to TNF-alpha, serine proteases, or reactive nitrogen intermediates, but is closely associated with a 170 kDa glycoprotein composed of two subunits with Mr's of 110 and 58 kDa.
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PMID:Characterization and partial purification of a high molecular weight tumoricidal activity secreted by murine bone marrow macrophages. 162 98

Mucin-specific lectin from Sambucus sieboldiana (SSA-M) reacts in Western blotting and ELISA with mucins from porcine stomach, bovine and ovine submaxillary glands, the human milk fat globule membrane, in vitro human ovarian, breast and colonic tumor cell lines, and mucins produced in vivo in the ascites of patients with endometrial and ovarian tumors, but not with fetal bovine fetuin or human transferrin. Sialidase treatment of these mucins led to an increase in the binding of SSA-M, suggesting that sialic acid is not part of the binding site for this lectin. Furthermore, sialic acid did not inhibit lectin binding. Treatment of asialomucin with O-glycanase decreased the binding of SSA-M, confirming the reactivity of the lectin with an O-linked carbohydrate. Treatment of mucins with trifluoromethanesulfonic acid, which removes all but core carbohydrate, led to an increase in the binding of SSA-M, suggesting that the lectin reacts with O-linked core glycans. Indeed, the increased reactivity after sialidase treatment of ovine submaxillary mucin suggests the lectin reacts with peptide-linked N-acetylgalactosamine (GalNAc), since more than 98% of the glycan chains attached to this mucin are sialylated GalNAc. The binding of SSA-M to sialidase-treated porcine mucin was inhibited strongly by GalNAc and disaccharides containing galactose (lactose, melibiose, and N-acetyllactosamine) but not by free galactose (Gal), suggesting that the glycan for optimum binding is Gal beta(1-3)GalNAc. This pattern of inhibition was different to other core glycan-reactive lectins tested, indicating that SSA-M is distinct, and should be of use in the isolation and characterisation of mucins and O-linked glycans.
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PMID:Reactivity of mucin-specific lectin from Sambucus sieboldiana with simple sugars, normal mucins and tumor-associated mucins. Comparison with other lectins. 166 64


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