Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After the observation that human mAb 32-27M reacts only with melanoma and astrocytoma cells cultured in the presence of fetal bovine serum, a novel pathway for the uptake of exogenous gangliosides, their further biosynthesis, and expression at the cell surface as novel Ag has been elucidated. The addition of fetal bovine serum to melanoma and astrocytoma cells growing in synthetic medium (insulin-transferrin-selenium) resulted in reactivity with Ab32-27M. As antibody 32-27M detects N-glycolylneuraminic acid (NeuGc)-containing gangliosides, the effect of adding a number of different gangliosides to melanoma and astrocytoma cells cultured in the synthetic medium was studied. Only the addition of NeuGc-GM3 resulted in the development of Ab32-27M reactivity. The identity of the antigenic structures developed after addition of fetal bovine serum or NeuGc-GM3 was determined by analysis of the gangliosides from both samples. The major component detected in melanoma cell lines was shown to be N-acetylneuraminic acid-NeuGc-GD3. Another, slower moving component, present in some melanomas and in astrocytomas may be N-acetylneuraminic acid-NeuGc-GD2. The cell type specificity for these processes can be most readily explained by postulating that all cells can take up exogenous gangliosides but only melanoma and astrocytoma cells have sufficiently high levels of GM3 alpha 2----8-sialyltransferase for the conversion of added NeuGc-GM3 to disialogangliosides to be effective. These results demonstrate a novel pathway for exogenous glycolipid processing that can lead to novel Ag expression but may also play a role in normal glycolipid metabolism and function.
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PMID:The addition of exogenous gangliosides to cultured human cells results in the cell type-specific expression of novel surface antigens by a biosynthetic process. 246 27

In this article, we summarized syngeneic monoclonal antimelanoma antibodies and their application for chemical characterization of mouse melanoma antigens, cloning of genomic DNA controlling antigen expression, and in vivo/in vitro tumor diagnosis. The melanoma antigen is composed of a protein complex in association with GM3(NeuAc)-like sugar moiety. The GM3 structure expresses the cross-species epitopes shared in various mammalian species, whereas the mouse specific melanoma epitope is present on protein molecules. By using the monoclonal antimelanoma reactive with GM3 epitope, we developed a very sensitive sandwich radioimmunoassay system detecting soluble melanoma antigens equivalent to 10(2)-10(3) cells/ml. The antibody was also useful in imaging tumor in vivo. These results indicate that the antibody with cross-species reactivity has a potential for tumor targeting. The monoclonal antibody M562 recognizing protein molecule with species specific epitope but not other antimelanoma antibodies, however, effectively inhibited experimental lung metastasis of melanoma cells, indicating that the M562 epitope seems to possess important biological functions. Recently, the genomic DNA controlling the antigen expression was successfully isolated by DNA transfection and expression technique with monoclonal anti-melanoma M562 and the fluorescence-activated cell sorter. We also found that genomic DNA possesses transformation-related activity in NIH3T3 cells.
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PMID:Syngeneic monoclonal antimelanoma antibodies and their application for analysis of tumor antigens, gene cloning, and in vitro/in vivo diagnosis. 247 34

In order to investigate GM2 expression in gliomas, the GM2-positive human glioma cell line (HGL) D-54 MG, which contains 0.6 nmol GM2/mg protein, representing 77% of the total monosialoganglioside fraction, was used as an immunogen for the production of anti-GM2 monoclonal antibodies. For ganglioside designations, see IUPAC-IUB (Eur. J. Biochem., 79: 11-21, 1977) and Svennerholm (J. Neurochem., 10: 613-623, 1963). Five IgM monoclonal antibodies (DMAb-1 through DMAb-5) specifically recognizing the GalNAc beta1-4(NeuAc alpha 2-3)Gal-terminal epitope common to GM2 and GalNAC-GD1a are reported. The antibodies did not react with GM1, GM3, GD2, GD3, GD1a, GD1b, and GQ1b. Purified anti-GM2 MAbs were used to define the expression of the "GM2" terminal epitope by cultured human malignant and normal cells by radioimmunoassay and membrane immunofluorescence. Among neuroectodermal tissue-derived cell lines, DMAb-3, at an optimal concentration of 5 micrograms/ml, showed high reactivity (radioimmunoassay binding ratios greater than 20) with 9 of 19 HGLs, 3 of 5 medulloblastoma, 4 of 5 neuroblastoma, and 1 of 3 melanoma lines. Moderate reactivity (binding ratio, 10-20) was exhibited by 3 HGL, 2 medulloblastoma, and 1 neuroblastoma lines and low reactivity (binding ratio, 3-10) by 5 HGL lines; no reactivity was detected with 2 HGL and 2 melanoma lines. Densitometric evaluation of monosialoganglioside extracts from human glioma and medulloblastoma cell lines in conjunction with immunostaining on thin-layer chromatograms showed that GM2 represents the major monosialoganglioside in 8 of 10 HGL and in 3 of 4 Med lines. In these lines the amount of GM2 ranged from less than 0.1 to 0.6 nmol/mg protein. These results indicate that GM2 represents a proportionally increased ganglioside of most glioma, medulloblastoma, and neuroblastoma cells in vitro.
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PMID:Five new epitope-defined monoclonal antibodies reactive with GM2 and human glioma and medulloblastoma cell lines. 247 68

Incubating B16 melanoma cells with an inhibitor of glucosylceramide (GlcCer) synthetase, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-threo-PDMP), led to a considerable decrease in the levels of GlcCer and lactosylceramide (LacCer). The content of ganglioside GM3 was little affected, but the ability to bind a monoclonal antibody against the ganglioside (M2590) was greatly reduced, suggesting that the reduction in the simple glycolipids led to encryption of the membrane antigen. This interpretation is supported by the observation that permeabilization of the treated cells with Triton X-100 restored immunological reactivity. Specificity of the PDMP effect was shown by its lack of effect on the reactivity of two other surface antigens to anti-melanoma monoclonal antibodies M562 and M622, and of the major histocompatibility antigens to anti-H-2KbDb monoclonal antibody. The ability of the treated cells to attach to laminin or type IV collagen was lost but that to fibronectin was not. The effects of the enzyme inhibitor were counteracted by including GlcCer in the culture medium. This indicates that the lipid was absorbed by the cells and utilized like endogenously-formed GlcCer. Cells preattached to laminin or collagen could be induced to round up by addition of inhibitor. In contrast, L-threo-PDMP (which does not block the synthesis of GlcCer) had no effect on the immunologic reactivity of GM3 or the adhesion properties of the cells. However, it did produce considerable accumulation of LacCer. These data suggest that the simple glycolipid, GlcCer, is an essential factor for antigenic expression of the more complex glycolipids on cell surfaces and that there is a close association and interaction between glycolipids and adhesive receptors on the cell surface.
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PMID:Effects of D-threo-PDMP, an inhibitor of glucosylceramide synthetase, on expression of cell surface glycolipid antigen and binding to adhesive proteins by B16 melanoma cells. 253 51

We attempted to induce anti-melanoma cytotoxic T cells (CTL) and suppressor T cells (Ts) inhibiting CTL generation by using liposomes carrying various densities of GM3 as tumor antigens. We found that liposomes carrying 6-16 mol% of GM3 with normal primary structure successfully generated anti-melanoma CTL and suppressor T cells, while liposomes with GM3 outside this range had little or no such activity. Anti-melanoma CTL induced by GM3(NeuGc)-liposomes belonged to CD4-/CD8- double-negative CD3+ CTL while GM3(NeuAc)-liposomes induced two types of T cells, CD4+ T cells and double-negative I-J positive T cells which mediated inhibition of the induction of anti-melanoma CTL responses. These cell types were the same as those induced by mitomycin C-treated melanoma cells for CTL induction and soluble melanoma antigen for Ts generation. The results clearly demonstrate that even GM3 with normal primary structure can, at a certain density, generate melanoma antigenicity.
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PMID:Density of GM3 with normal primary structure determines mouse melanoma antigenicity; a new concept of tumor antigen. 253 93

We have shown that a syngenic monoclonal antibody, M2590, established after immunization of C57BL/6 mice with B16 melanoma cells, recognized GM3 (NeuAc) ganglioside. Although GM3 is widely distributed among various normal cells and tissues, the antibody did not react with them. However, it reacted exclusively with melanoma cells from mouse, hamster and human. Preliminary experiments suggested that proteins and lipids as well as GM3 density on B16 cells are involved in the reactivity of GM3 with the antibody. Then, we investigated the biological function of the melanoma antigen, which was secreted from B16 cells into the culture medium. This soluble antigen was shown to suppress the positive immune responses by inhibiting CTL activity in the effector phase and by induction of specific suppressor T cells (Ts) that block CTL generation in the induction phase. Liposomes containing GM3 (NeuAc) but not GM3 (NeuGc) can effectively induce the melanoma specific Ts as did the soluble antigen. The results indicated the tumor cells can escape from host-immune system by stimulating the repertoire of Ts for self-antigen, GM3. To understand the biological role of GM3, we have established mutant clones of no-expressor of GM3 recognized by M2590. The clones were found to have lower attachment to laminin and type IV collagen and poor ability of lung metastasis.
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PMID:[GM3 ganglioside as melanoma specific antigen and its biological function]. 253 60

The glycosphingolipid compositions of Bomirski melanomas at different stages of differentiation, including Ab amelanotic melanoma (fast growing), Ma melanotic melanoma (slow growing), and MI hypomelanotic melanoma (slow growing), were studied. The total concentration of lipid-bound sialic acid in Ab amelanotic melanoma was found to be much lower than those in Ma and MI melanomas (0.8 micrograms versus 1.4 micrograms and 1.4 micrograms/mg of dry tissue, respectively). The ganglioside patterns in melanoma tissues were composed mainly of three components, which were confirmed as NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer (GM3), acetyl1-9-O-NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer (9-O-acetyl-GD3), and NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer(GD3) by structural analysis and monoclonal antibody detections. However, the relative ratios of these gangliosides expressed in the different types of melanomas were completely different. The MI melanoma tissues contained GM3 as the predominant species (greater than 90% of the total gangliosides) with very little of GD3 and 9-O-acetyl-GD3 gangliosides (less than 2% of the total gangliosides). In contrast, Ab amelanotic melanomas contained mainly 9-O-acetyl-GD3 (greater than 27%) and GD3 (greater than 51%) with lesser amounts of GM3. However, Ma melanoma had intermediate levels of GM3, GD3, and 9-O-acetyl GD3. The MI and Ma melanomas also contained monohexosylceramide (GL1) (about 60% as Gal beta 1-1'Cer and 40% as Glc beta 1-1'Cer in Ma and 30% as Gal beta 1-1'Cer and 70% as Glc beta 1-1'Cer in MI) and Gal beta 1-4Glc beta 1-1'Cer as the predominant neutral glycosphingolipid species. In contrast, Ab melanoma tissues contained more GalNAc beta 1-3GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc beta 1-1'Cer (Gb5), Gal alpha 1-4Gal beta 1-4Glc beta 1-1'Cer (Gb3), and GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc beta 1-1'Cer (Gb4) than MI and Ma melanomas. Our data suggest that the expression of glycosphingolipids in hamster melanoma cells may be closely related to cell growth and the degree of differentiation, with slow growing, highly differentiated cells expressing GM3 and GL1, and fast growing, undifferentiating cells having a preponderance of GD3, 9-O-acetyl-GD3, Gb5, Gb3, and Gb4.
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PMID:Glycosphingolipids in Bomirski transplantable melanomas in hamsters. 258 47

In view of the possible role of glycosphingolipids in defining the specificity of cell-cell interactions, the key molecules for recognition of cell surface glycosphingolipids have been studied. In addition to previously suggested recognition mechanisms involving endogenous lectins and glycosyltransferases, an alternative possibility, based on carbohydrate-carbohydrate (Lex-Lex) interaction, has been raised (Eggens, I., Fenderson, B., Toyokuni, T., Dean, B., Stroud, M., and Hakomori, S. (1989) J. Biol. Chem. 264, 9476-9484). We now report a highly specific interaction between gangliotriaosylceramide (Gg3, GalNAc beta 1----4Gal beta 1----4Glc beta 1----Cer) and sialosyllactosylceramide (GM3, NeuAc alpha 2----3Gal beta 1----4Glc beta 1----Cer). The interaction requires a bivalent cation (Ca2+ or Mg2+) and can be inhibited by sialosyl 2----3 lactose, anti-GM3 antibody (DH2), anti-Gg3 antibody (2D4), or EDTA. The strength of interaction between GM3 liposome and the Gg3-coated plastic surface was highly density-dependent. The mouse lymphoma L5178 AA12 cell line (high expressor of Gg3) interacted specifically with the mouse B16 melanoma cell line (high expressor of GM3). The interaction was inhibited by 5 mM sialosyllactose, anti-GM3 antibody, anti-Gg3 antibody, and EDTA in analogy to GM3-Gg3 interaction. L5178 AV27, a genetically related variant clone which does not express Gg3, showed no interaction with B16 cells. Untreated AA12 cells, but not 2D4-treated AA12 cells or AV27 cells, interacted with GM3 coated on the plastic surface. These findings suggest a specific interaction between AA12 cells and B16 cells based on Gg3-GM3 interaction.
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PMID:Specific interaction between gangliotriaosylceramide (Gg3) and sialosyllactosylceramide (GM3) as a basis for specific cellular recognition between lymphoma and melanoma cells. 258 11

Seven monoclonal antibodies (mAbs) reactive with ganglioside II3(NeuAc)2-LacCer (GD3) were generated; four of these mAbs (DMAb-21, DMAb-22, DMAb-23, and DMAb-24) by immunizing mice with GD3 adsorbed to Salmonella minnesota and the remaining three (DMAb-7, DMAb-8, and DMAb-17) with melanoma line SK-MEL 28, which contains 1.4 nmol sialic acid of GD3 per mg protein. The specificities of the mAbs were defined by high-performance thin-layer chromatography (HPTLC) immunostain and solid-phase radioimmunoassay (SP-RIA) with a panel of purified gangliosides. DMAb-7 and DMAb-8 reacted with GD3, IV3(NeuAc)2nLcOse4Cer(3',8'-LD1), and very weakly with IV3(NeuAc)2II3NeuAcGgOse4Cer (GT1a), but not with II3NeuAc-LacCer (GM3), II3NeuAcGgOse3Cer(GM2), II3NeuAcGgOse4Cer (GM1), II3NeuAc, IV3NeuAcGgOse4Cer (GD1a), II3(NeuAc)2GgOse3(GD2), II3(NeuAc)2GgOse4Cer (GD1b), IV3NeuAcII3(NeuAc)2, GgOse4Cer(GT1b), suggesting the binding epitope to be a terminal tetrasaccharide NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-4(Glc or GlcNAc). DMAb-7 and DMAb-8 were used to investigate the expression of GD3 on cultured human tumor cells of neuroectodermal origin. Thirteen of 19 gliomas, 3 of 5 medulloblastomas, 5 of 5 neuroblastomas, 2 of 2 melanomas, and 1 of 3 teratomas were shown to react with DMAb-8 and/or DMAb-7 by cell surface-RIA (CS-RIA) and immunofluorescence (IF) assays. HPTLC and densitometric analysis confirmed these results, as positive immunostains in the GD3 region were obtained with oligoganglioside fractions from 9 glioma, 1 medulloblastoma, 2 neuroblastoma, 1 melanoma, and 1 teratoma cell line. Glioma cell line U-105 MG and medulloblastoma cell line Daoy contain GD3 as shown by HPTLC immunostain analysis of extracts, although GD3 was undetectable on the cell surface as determined by CS-RIA and IF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:GD3 expression by cultured human tumor cells of neuroectodermal origin. 260 39

The present study investigates the chemical structure of a ganglioside, detected by monoclonal antibody (MAb) MacG1, which reacts with intracytoplasmic granules of tumor-infiltrating macrophages. The results obtained by enzymatic hydrolysis and fast-atom bombardment-mass spectrometry reveal that MAb MacG1 reacts with a subcomponent of the ganglioside GM3 found in melanoma and bovine brain. MAb MacG1 might be a powerful tool to distinguish among GM3 species and could help to define their possibly different biological functions.
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PMID:Monoclonal antibody MACG1 distinguishes between different molecular species of the ganglioside GM3. 271 13


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