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)

The ganglioside composition of human malignant melanoma was studied with the use of 80 melanoma specimens, including 52 surgical specimens and 28 cultured cell lines. A ganglioside fraction was isolated and purified from each of these tissues, and the amount of each component ganglioside was assessed by thin-layer chromatography (TLC) and a TLC scanner. Five gangliosides (GM3, GD3, GM2, GD2, and alkali-labile ganglioside) were most commonly expressed by these melanomas. However, the total ganglioside amount (ranging from 33 to 302 micrograms/g wet wt of tissue) as well as the distribution of each ganglioside were widely heterogeneous in both biopsied and cultured melanomas. When the ganglioside expressions of cultured and biopsied melanomas were compared, GM2 and GD2 were minor components of biopsied melanomas but often became major components of cultured melanoma cells. Conversely, alkali-labile ganglioside was expressed more strongly on biopsied melanomas. This heterogeneity suggests that it will be necessary to analyze the ganglioside composition of biopsied melanomas before using monoclonal antibodies to melanoma-associated gangliosides for melanoma diagnosis or therapy.
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PMID:Gangliosides of human melanoma. 346 29

An increased synthesis of the ganglioside GM2 has been reported on transformed murine cells, human fetal tissues, and transformed melanocytes. This study was designed to investigate whether any correlation existed between GM2 expression and the tumorigenicity of human melanoma. Ten established human melanoma cell lines, 5 rich in GM2 (group A) and 5 poor in GM2 (group B), were selected on the basis of previous ganglioside analysis of 28 melanoma cell lines. Six athymic nude mice per cell line were given an sc injection of 10(6) human melanoma cells/mouse. Tumors were measured every 2-4 days. By day 36 after the injection, 28 of 30 mice (93%) in group A developed medium to large tumors, but only 1 of 30 (3%) in group B developed a small tumor (P less than .005). The correlation of GM2 content of individual melanomas with tumor growth rate also was very high. GM2 content was expressed as nanomoles per gram wet weight of each melanoma. The area under the log values of tumor growth curves from day 0 to day 36, which represented tumor growth rate, tumor size, and latent period, was proportional to GM2 content, with a correlation coefficient of 0.927 and with P less than .001. The same log relationship when tested with other gangliosides, GM3, GD3, and GD2, was not statistically significant. These results, combined with the fact that variations in GM2 content do not affect in vitro growth of human melanoma cells, suggest that GM2 expression may be directly related to the dedifferentiation or the tumorigenicity of human melanoma.
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PMID:Gangliosides of human melanoma: GM2 and tumorigenicity. 346 30

A monoclonal antibody, M2590, that recognizes hematoside (GM3) was used to analyze the immunostaining localization of GM3 of the surface of transformed and non-transformed hamster embryo fibroblasts and B16 melanoma cells. The reactivity of GM3 with the antibody changed markedly depending on the cell density. At the sparse density cells were clearly made visible by the antibody, but at the confluency the accessibility of the antibody to GM3 was greatly decreased. This density dependent change in the reactivity of GM3 was found for both normal and transformed cells. The staining pattern of GM3 was examined in relation to the actin fibers made visible with NBD-Phallacidin during cell spreading. When the cells were still round, the GM3 on microspikes or blebs was highly reactive with the antibody, and by the time cells showed circumferential staining of their actin fibers, GM3 had been distributed over the entire cell surface as punctuated spots. GM3 also was visible in substrate attachment materials (SAM). Trypsin treatment of SAM diminished the reactivity of GM3 with the antibody. The antibody did not inhibit cell attachment or spreading on a substratum coated with fibronectin or laminin.
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PMID:Change in the topographical distribution of GM3 during cell spreading and growth: immunostaining with monoclonal antibody against GM3. 356 53

A murine monoclonal antibody (mAb), designated mAb 202, was generated using a human melanoma cell line, UCLASO-M14 as the immunogen. mAb 202 reacted with two (GM2 and GM3) of the four (GM2, GM3, GD2, and GD3) gangliosides expressed by M14. Several authentic monosialogangliosides, including GM4, GM3, GM2, GM1, GM1b, and sialylparagloboside were then tested for their binding to 202 mAb by the immune adherence inhibition assay, TLC-enzyme immunostaining, and enzyme-linked immunosorbent assay. All showed positive binding but in varying degrees. GM4 showed the strongest affinity. No significant differences of reactivity were observed between the sialic acid derivatives, N-acetyl and N-glycolyl, in these gangliosides. Disialogangliosides such as GD3, GD2, GD1a, and GD1b, trisialoganglioside GT1b, and neutral glycolipids including GlcCer, GalCer, LacCer, GbOs3Cer, GbOs4Cer, GgOs3Cer, GgOs4Cer, and nLcOs4Cer were all negative. These results indicate that the 202 mAb detects sialyl alpha 2----3Gal residue in the monosialoganglioside, irrespective of the internal structure. Since GM4 is not expressed by M14 cells, the terminal disaccharide (sialyl alpha 2----3Gal) in GM3 and/or GM2 must have been the epitope responsible for the generation of the antibody.
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PMID:Monoclonal antibody detects monosialogangliosides having a sialic acid alpha 2----3-galactosyl residue. 357 Dec 88

A mouse monoclonal antibody M2590, previously established after immunization of mice (C57BL/6) with syngeneic melanoma B16 cells and showing preferential reactivity with various types of melanoma over other tumor and normal cells or tissues, was shown to be directed to GM3 ganglioside. Since GM3 is widely distributed in essentially all types of animal cells, there is a conflict with the concept of a tumor-associated antigen and immunogen. Studies on the reactivity of M2590 antibody with various cells having different GM3 density at their cell surface, including cells treated with sialidase, liposomes, and solid-phase lipid layer containing different GM3 concentrations, have indicated that 1) reactivity of the antibody M2590 depends greatly on the density of GM3 exposed at the cell surface, on liposomes, or on solid phase; and 2) there is a threshold density that is recognized by the antibody in all-or-none fashion. In addition, the antibody M2590 reacts not only with GM3 but also with GM3 lactone, and the binding affinity of the antibody to GM3 lactone is strikingly higher than to GM3; however, the antibody does not react with GM3 ethyl ester. GM3 lactone was detected in melanoma as 3H-labeled GM3 gangliosidol after melanoma cells were directly treated with NaB[3H]4. A comparative immunization of BALB/c mice with GM3 and GM3 lactone showed that GM3 lactone is a much stronger immunogen than GM3, although the antibody elicited reacts with both GM3 and its lactone. Thus, the real immunogen could be GM3 lactone, although it is a minor membrane component.
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PMID:Density-dependent recognition of cell surface GM3 by a certain anti-melanoma antibody, and GM3 lactone as a possible immunogen: requirements for tumor-associated antigen and immunogen. 366 54

A mouse (C57BL/6) monoclonal antibody M2590, which is established against syngeneic melanoma B16 cells, reacted with chemically synthesized GM3. NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1' ceramide (24:0/d 18:1), but not with its stereoisomer, NeuAc beta 2-3Gal beta 1-4Glc beta 1-1' ceramide (24:0/d 18:1).
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PMID:Reactivity of mouse monoclonal antibody M2590 against B16 melanoma cells with chemically synthesized GM3 ganglioside. 394 May 32

The immunogenicity of gangliosides found on human melanoma cells was determined from sera of 26 melanoma patients who were immunized every 1-4 weeks for 4 months with tumor-cell vaccine (TCV) prepared from cultured melanoma cells. Total lipid-bound sialic acid in the gangliosides isolated from TCV was 0.38 mumol/10(8) cells, and was distributed as follows: 44.8% to GM3, 44.2% to GD3, 5.6% to GM2, and 4.6% to GD2. Sera were tested at monthly intervals for antibodies to each ganglioside by ELISA with purified gangliosides as the antigen source. The immunologic specificity of the antibody was confirmed by absorption tests. None of the 26 patients had detectable anti-GM3, anti-GD3, or anti-GD2 antibodies before immunization, although anti-GM2 antibody was detected in 3 patients. After immunization, 2 patients developed IgM anti-GD2, 10 developed IgM anti-GM2, and 2 developed IgG anti-GM2 antibodies. No patient developed detectable anti-GM3 or anti-GD3 antibodies. These results indicate that both GD2 and GM2 expressed on human melanoma cells are immunogenic in humans, although GM2 appears to be more immunogenic. The other two gangliosides, GM3 and GD3, are present in human sera and in human normal tissues, and thus immunologic tolerance may have been established against these gangliosides. Alternatively, circulating GM3 and GD3 may have neutralized anti-GM3 and anti-GD3 antibodies, if any were induced by TCV immunization.
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PMID:Immunogenicity of melanoma-associated gangliosides in cancer patients. 399 82

Normal melanocytes and melanocytes of normal nevi, primary melanoma in the radial (RGP) and vertical (VGP) growth phases, and metastatic melanoma exhibited and maintained phenotypic differences when grown in tissue culture or in experimental animals. Only metastatic and VGP primary melanoma cells were tumorigenic in athymic nude mice and had nonrandom chromosomal abnormalities involving chromosomes 1, 6, and 7. The colony-forming efficiency in soft agar was also highest in these two cell types. A cell line of RGP primary melanoma had characteristics of both benign and malignant cells: nevus-like morphology; nontumorigenicity in nude mice; but karyotypic abnormality of chromosome 6. It also had a ganglioside pattern similar to that of normal melanocytes but not melanomas, i.e., a high GM3 ganglioside content compared to the amounts of GM2, GD2, and GD3 gangliosides. Binding of monoclonal antibodies secreted by hybridomas generated by immunization of mice with VGP primary and metastatic melanoma was highest with cells and supernatants of cultures from advanced melanoma and least with nevus cells. There was no binding to normal melanocytes except with the monoclonal antibodies specific for nerve growth factor receptor or 9-O-acetyl-GD3 ganglioside. On the other hand, monoclonal anti-nevus antibodies bound to melanocytes, nevus cells, and RGP primary melanoma cells but not to VGP primary or metastatic melanoma cells. Cultured human melanocytic cells appear to be a unique model for the study of tumor progression.
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PMID:Characteristics of cultured human melanocytes isolated from different stages of tumor progression. 405 39

The major ganglioside component isolated from diploid human melanocytes is sialosyllactosylceramide (GM3 86-91% of total sialic acid). The corresponding disialo derivative (GD3) is found as a minor component (2-6% of total sialic acid) in the membranes of these cells. In human melanoma cells, grown in tissue culture, GD3 is the predominant ganglioside component (48-63% of total sialic acid). Withdrawal of TPA from the culture medium of normal melanocytes or addition of TPA to the medium of melanoma cells had no significant effect on GM3/GD3 ratios. We conclude that the difference between the composition of gangliosides is related to the normal vs transformed phenotypes of melanocytes.
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PMID:Gangliosides of normal and neoplastic human melanocytes. 673 68

Mouse monoclonal antibody AbR24 has a high degree of specificity for human melanoma cells when tested on viable cultured cells using the protein A mixed hemagglutinin serological assay. The antigen detected by this antibody has been isolated from melanoma cells and shown to be GD3 ganglioside by compositional and partial structural analysis and by comparison with authentic GD3 in thin layer chromatography (TLC). AbR24 reacts with authentic GD3, but not with any other ganglioside tested. Using TLC and reactivity with AbR24, a wide range of cells and tissues was examined for the presence of GD3. A new serological assay, termed glycolipid-mediated immune adherence, was devised for assaying the reactivity of AbR24 with gangliosides. Melanomas (cultured cells or tumor tissue) were shown to have GD3 and GM3 as major gangliosides. Other cells and tissues examined also contained GD3, but usually only in low amounts. Melanomas (and MOLT-4, a T cell line) were characterized by a simplified ganglioside profile with GD3 and GM3 as major components. The apparent discrepancy between the ubiquitous presence of GD3 and the serological specificity of AbR24 for melanoma cells can be explained in terms of localization and concentration of GD3 in different cells.
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PMID:GD3, a prominent ganglioside of human melanoma. Detection and characterisation by mouse monoclonal antibody. 706 53


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