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)

Ganglioside GM2 is expressed on cell surface membranes of a variety of human malignant cells and has been demonstrated to be immunogenic in humans. We have assessed the role of the antigen GM2 on melanoma cells as a recognition structure for lymphokine-activated killer (LAK) cells. LAK cells were generated by stimulation of non-adherent peripheral blood lymphocytes (PBL) from human donors with recombinant interleukin-2 (IL-2). The selection of target cells was based on GM2 content and included 11 human melanoma cell lines and 2 human leukemia lines. Using a single-cell binding assay, LAK cell binding to target lines expressing high levels of GM2 was significantly greater than to those expressing minimum GM2. This cell-binding was specifically inhibited by addition of purified GM2 but not by other gangliosides. LAK-melanoma cell-binding was also specifically inhibited by anti-GM2 monoclonal antibody (MAb). For further analysis LAK cell lysis of melanoma target cells expressing various amounts of GM2 was assessed. A significant correlation occurred with GM2 expression and LAK cell lysis (p less than 0.025; r = 0.623). Three other gangliosides commonly expressed on human melanoma, GM3, GD3 and GD2, had no correlation with LAK cell lysis. These studies suggest that GM2 on melanoma cells is a marker for LAK cell sensitivity, as well as indicate that GM2 is a potential target recognition structure for human LAK cells.
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PMID:Ganglioside GM2 expression on human melanoma cells correlates with sensitivity to lymphokine-activated killer cells. 271 90

The immunogenicity of the disialoganglioside, GD3, a melanoma-tumor-associated antigen, has been evaluated in non-human primates. Sera from four chimpanzees and two monkeys were evaluated for anti-GD3 antibody activity by solid-phase radioimmunoassay using GD3 and control gangliosides as targets. Serum from one monkey, immunized with cells from a melanoma cell line, was strongly reactive with GD3, having a titer of greater than 2500. In contrast, serum from this animal was non-reactive with several other gangliosides including the structurally similar GM3. Anti-GD3 reactivity was also demonstrable, albeit in low titer, in the sera of an additional monkey and a chimpanzee. Each of these animals had likewise been immunized using cells from melanoma cell lines. On the basis of these observations, suggestive of a primate anti-GD3 antibody response, we initiated a series of immunizations of chimpanzee using purified GD3 bound to Salmonella minnesota, R595. IgG reactive with melanoma cells in the cell-binding assay was first detected in sera collected after 4 immunizations and increased in titer against each reactive melanoma cell line during the immunizations. Reactivity of this serum with melanoma cell lines demonstrated a direct correlation with the expression of GD3 by the respective cell line. Anti-GD3 reactivity was evident in solid-phase radioimmunoassay against purified GD3 beginning with serum collected after 11 immunizations. By comparison with its binding to the control ganglioside panel, this serum demonstrated strong specificity for GD3 (titer = 640) while having only marginal reactivity with GM3 (titer = 40). Immune serum from this animal was also able specifically to block subsequent binding of a murine IgM anti-GD3 antibody (DMab7) to target GD3 in solid-phase radioimmunoassay. Together, these observations suggest that GD3, in the form of a purified molecule bound to a bacterial matrix or as part of the intact melanoma cell membrane, can be immunogenic in non-human primates, and is able to elicit an antibody response of appropriate specificity.
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PMID:Serological response of non-human primates to human melanoma disialoganglioside GD3. 273 Nov 85

Gangliosides appear to be important target molecules for immunological effector mechanisms on neuro-ectodermal tumors. Therefore in vitro studies were performed to examine whether ganglioside GD3, which is highly expressed on the cell surface of cultured human melanoma cells, is being shed into the culture medium. Measurable quantities of gangliosides GM3 and in particular GD3 were shed by the melanoma cells we have tested as detected on thin-layer chromatograms (TLC) stained with orcinol. Ganglioside GD3 was also evidenced by immunostaining with anti-GD3 MAb and by ELISA. The concentration of GD3 in the supernatant of human melanoma cells depended on the ganglioside pattern of the cell line. Cells containing high levels of GD3 shed large amounts, cells with low levels shed no detectable GD3. Ganglioside GD3 was detectable in sera, but no major quantitative differences were observed in sera of patients with GD3-positive tumors and normal controls. This points to a local accumulation of ganglioside GD3 at the tumor site.
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PMID:Ganglioside GD3 shedding by human malignant melanoma cells. 274 85

In human tumors of neuroectodermal origin cell surface expression of individual gangliosides is either increased or decreased relative to comparable normal cells. We have previously shown that gangliosides shed from melanoma cells can immunomodulate T cell activity. Monocytes/macrophages (m/m) are known to play an important role as accessory and effector cells in immune responses. We therefore investigated the effect of exogenous gangliosides derived from melanoma on m/m functions in vitro. Gangliosides commonly expressed on human melanoma such as GM3, GD3, GM2, and GD2 were investigated, as well as GM1, a major component of human neural tissue. Monocytes were isolated from human peripheral blood mononuclear cell populations, treated with gangliosides in vitro, and evaluated in several functional assays. Treatment of m/m with GM2 and GM3 gave the greatest inhibition of Fc receptor expression. GM1 and GD3 on the other hand most inhibited the production of interleukin-1 (IL-1) by m/m. Production of tumor necrosis factor (TNF) like monocytoxin was not affected by incubation with individual gangliosides. These studies suggest that individual melanoma gangliosides have different regulatory effects on m/m functions.
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PMID:Modulation of human macrophage functions by gangliosides. 278

Human melanoma cells express high levels of GM3 and GD3 gangliosides whereas normal melanocytes have only low levels of GD3 but maintain their expression of GM3. In order to understand the basis for this difference, the levels of the sialyltransferase that converts GM3 to GD3 (CMP-N-acetylneuraminic acid:GM3 sialyltransferase or GD3 synthase, EC 2.4.99.8) were analyzed in melanoma and other cell lines. Enzyme levels were determined in vitro using membrane preparations and measuring the addition of [14C]-N-acetylneuraminic acid from CMP-[14C]-N-acetylneuraminic acid to GM3 in the presence of Triton CF-54. Sialyltransferase levels in 44 human cancer cell lines (including melanoma, neuroblastoma, astrocytoma, various carcinomas, and leukemias) and cultures of normal melanocytes and kidney epithelial cells were compared, and the products were identified by thin layer chromatography and fluorography. Melanoma cell lines exhibited the highest levels of incorporation and GD3 was found to be the major product. GM3 was also formed, apparently from endogenous lactosylceramide. Very low levels of GD3 synthase were found in normal melanocytes. Neuroblastoma and some astrocytoma cell lines also had significant levels of GD3 synthase. Some other cell lines incorporated high levels of radioactivity but the products did not correspond to GD3 and the major product was usually GM3. In general the levels of GD3 synthase correlated with the expression of GD3 in the various cell types. These results point to higher levels of GD3 synthase being directly responsible for the enhanced expression of GD3 in melanoma.
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PMID:Sialyltransferase levels and ganglioside expression in melanoma and other cultured human cancer cells. 280 71

A novel ganglioside, de-N-acetyl-GM3 (neuraminyllactosylceramide, II3NeuNH2LacCer), was found in the monosialoganglioside fraction of A431 cells and B16 melanoma cells by high-performance liquid chromatography, thin-layer chromatography, and immunoblotting with its specific monoclonal antibody DH5. This novel type of membrane ganglioside strongly enhanced the kinase activity associated with the epidermal growth factor (EGF) receptor, and it showed 32, 35, and 12% growth stimulation as compared with control cultures of A431, Swiss 3T3, and B16 melanoma cells, respectively. Exogenously added de-N-acetyl-GM3 did not alter the affinity of EGF binding to its receptor. These properties of de-N-acetyl-GM3 are in striking contrast to those of GM3 and its lyso derivative (lyso-GM3) which were previously shown to inhibit EGF receptor kinase activity and to inhibit growth in the same cells. These data indicate that de-N-acetylation at the sialic acid moiety of GM3 ganglioside is an important mechanism for modulation of EGF-dependent cell growth. The mechanism is antagonistic to that of GM3-dependent modulation of receptor function.
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PMID:A novel ganglioside, de-N-acetyl-GM3 (II3NeuNH2LacCer), acting as a strong promoter for epidermal growth factor receptor kinase and as a stimulator for cell growth. 283 72

The fine specificity analysis of two human monoclonal antibodies (AbFCM1 and AbHJM1) reacting with gangliosides is described and their specificities are compared with analogous mouse monoclonal antibodies (mAbs). These two antibodies were generated from lymphocytes of melanoma patients by Epstein-Barr virus transformation followed by fusion with mouse myeloma NS-1. Using a wide variety of gangliosides, including N-glycolylneuraminic acid (NeuGc)-containing compounds, the precise structures recognized by these two antibodies were elucidated by enzyme-linked immunosorbent assay and immunostaining of thin-layer chromatograms. AbFCM1 reacted with N-acetylneuraminic acid (NeuAc)-type GM3, GD1a, sialylparagloboside, and GT1b in decreasing order of intensity. This antibody also reacted with (NeuAc-NeuGc-)-GD3 and -disialylparagloboside, but did not react with NeuGc-type GM3, GM2, sialylparagloboside, (NeuGc)2-GD3 and -disialylparagloboside. The main epitope structures recognized by AbFCM1 are, therefore, NeuAc alpha 2----3Gal beta 1- and NeuAc alpha 2----8NeuGc alpha 2----Gal beta 1-. These results are similar to the specificity of mouse mAb M2590. AbHJM1 reacted with NeuAc-type GD3 and disialylparagloboside, GD2, GD1b, GM3, and GT1b, in decreasing order of intensity. Among NeuGc-type gangliosides, this antibody reacts with (NeuAc-NeuGc-)-GD3 and -disialylparagloboside, but did not react with gangliosides containing only NeuGc. Consequently the epitope structure recognized by AbHJM1 is probably (R)-(NeuAc alpha 2----8Sialic acid alpha 2----3)Gal beta 1-. Mouse anti-GD3 mAbR24, in contrast, showed strong reactivity only with GD3 and -disialylparagloboside among NeuAc-type gangliosides, but showed a similar pattern to AbHJM1 in its reactivity with NeuGc-containing gangliosides. Although these two human monoclonal antibodies are not highly restricted in their specificities, they reacted best with the major gangliosides, GM3 and GD3, present in the majority of human melanomas.
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PMID:Two human monoclonal antibodies reacting with the major gangliosides of human melanomas and comparison with corresponding mouse monoclonal antibodies. 290 45

Human melanoma synthesizes a large quantity of gangliosides, glycosphingolipids containing sialic acid. The authors previously have demonstrated that the ganglioside profile differs among individual melanomas and is widely heterogeneous. In the current study, a retrospective study was performed to compare the relationship between the quantity of five major gangliosides of human melanoma (GM3, GM2, GD3, GD2, and alkali-labile ganglioside) and nine clinical factors (sex, age, site, stage, tumor size, pigmentation, histopathologic type of primary tumor, chemosensitivity, and prognosis). Melanoma specimens studied were obtained from patients of our clinic and included 52 biopsy specimens and 28 cultured cell lines. Analysis of melanoma biopsy specimens have shown a differential ganglioside expression among different sites of tumor, pigmentation, and histopathologic types. Results of cultured melanoma cell lines differed from those of biopsy specimens, but ganglioside expression also differed among the site of tumor, tumor size, histopathologic types, and chemosensitivity. GM3 positively correlated with a good prognosis in both biopsy and cultured melanomas.
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PMID:Gangliosides of human melanoma. 291 20

The immunological and chemical properties of melanoma antigens have been analysed by using C57BL/6-derived B16 melanoma cells. CTL was easily induced by the antigen of the melanoma cell surface, whereas soluble antigens secreted into the culture supernates worked as a specific inducer substance of suppressor T cells. Using two syngeneic monoclonal anti-melanoma antibodies (M2590, M562), we found that the melanoma antigen was composed of GM3 (NeuAc) in association with proteins with molecular weights of 31K, 58K and 80K. M2590 detected GM3, whereas M562 recognized the protein determinant. Finally, we succeeded in cloning the genomic DNA which codes for the melanoma antigen. The B16-melanoma cosmid libraries were constructed with the shuttle vector pCV103. They were infected into ED8767 E. coli and then transfected into human P36 melanoma by protoplast fusion. The transfectants were selected in the presence of mycophenolic acid, strained with FITC-M562, and selected by FACS. Total DNA was isolated from the transfectants, and the B16 genomic clones were rescued from the M562+ transfectants by in vitro packaging with lysogenic bacterial extracts. pD2-7 (34.8kb) reproducibly expressed M562 determinants in P36 human melanoma.
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PMID:[Mouse melanoma antigen immunological properties, structure and genes]. 293 47

Melanoma antigen was characterized by using the C57BL/6 mouse melanoma (B16) system, especially in relation to escape mechanisms of tumor cells from immunological surveillance. The antigen on the surface of melanoma cells selectively induced double negative cytotoxic T lymphocytes (CTL) lacking genetic restriction specificity in their action, whereas the soluble antigen shed or secreted from the cells preferentially induced suppressor T cells (Ts) inhibiting CTL generation in the induction phase. The epitopes of melanoma antigen for CTL and Ts were found to possess a "GM3-like structure". Anti-melanoma CTL activity was blocked by either GM3(NeuAc)-or GM3(NeuGc)-liposomes. Moreover, the GM3 (NeuGc)-liposome could induce anti-melanoma CTL when used as an antigen in the in vitro primary response. On the other hand, the soluble melanoma antigen or GM3(NeuAc)-but not GM3(NeuGc)-liposome itself specifically induced anti-melanoma Ts. Therefore, anti-melanoma Ts are able to distinguish GM3 molecular species. We also found two types of T cells, C3T4+ and double negative I-J+ T cells, to be involved in this suppression. Although the primary structure of melanoma GM3 was demonstrated to be the same as that of normal GM3, syngeneic anti-melanoma GM3 monoclonal antibody (M2590) did distinguish melanoma from normal cells. Further close analysis in liposome lysis experiments using various concentrations of GM3 clearly demonstrated that M2590 anti-melanoma GM3 only reacted with GM3 at a "high" density (more than 10-12 mol%), whereas no reactivity was observed at a "low" density (less than 7.5 mol%). It is clear, therefore, that the density of GM3 with normal primary structure is important in generating melanoma antigenicity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of melanoma antigen and its involvement in tumor-escape mechanisms. 297 19


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