Gangliosides as antigens of human melanoma

  • Mepur H. Ravindranath
  • Reiko F. Irie
Part of the Cancer Treatment and Research book series (CTAR, volume 43)


Gangliosides, the glycosphingolipids containing sialic acids, are fundamental constituents of vertebrate cells [1]. Gangliosides are located on the cell membrane, with the carbohydrate moiety exposed outside the cell surface and the lipid portion embedded in the bilayer lipid membrane. Gangliosides are most abundant in neural tissues but are also found in small quantities in other cells [2, 3]. Many different types of gangliosides have been identified in human tissues. The ganglioside composition differs among different normal tissues as well as among different forms of cancers.


Melanoma Cell Sialic Acid Melanoma Patient Melanoma Cell Line Human Melanoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Weigandt H: Glycolipids. Amsterdam: Elsevier, 1985; p. 314.Google Scholar
  2. 2.
    Ando S: Gangliosides in the nervous system. Neurochem Interntl 5:507–537, 1983.CrossRefGoogle Scholar
  3. 3.
    Sastry PS: Lipids of nervous tissue: Composition and metabolism. Prog Lipid Res 24:69–176, 1985.PubMedCrossRefGoogle Scholar
  4. 4.
    Tsuchida T, Saxton RE, Morton DL, and Irie RF: Gangliosides of human melanoma. J Natl Cancer Inst 78:45–54, 1987.PubMedGoogle Scholar
  5. 5.
    Irie RF, Morton DL: Regression of cutaneous metastatic melanoma by intralesional injection with human monoclonal antibody to ganglioside GD2. Proc Natl Acad Sci USA 83:8694–8698, 1986.PubMedCrossRefGoogle Scholar
  6. 6.
    Roitt I, Brostoff J, Male D: Immunology. St. Louis: C.V. Mosby, 1985.Google Scholar
  7. 7.
    Schauer R: Analysis of sialic acids. Methods Enzymol 138:132–161, 1987.PubMedCrossRefGoogle Scholar
  8. 8.
    Svennerholm L: The gangliosides. J Lipid Res 5:145–155, 1964.PubMedGoogle Scholar
  9. 9.
    Hakomori S: Monoclonal antibodies directed to cell-surface carbohydrates. In: Monoclonal antibodies and functional cell lines, Kenneth RH, Bechtol K-B, McKearn TJ (eds). New York: Plenum Press, 1984, pp. 67–100.Google Scholar
  10. 10.
    Paulson JC: Interactions of animal viruses with cell surface receptors. In: Receptors, M Conn (ed). New York: Academic Press, Vol. 2, 1985, p. 131.Google Scholar
  11. 11.
    Bergelson LD, Bukrinskaya AG, Prokazova NV, Shaposhnikova GI, Kocharov SL, Shevchenko VP, Kornilaeva GV, Fomina-Ageeva EV: Role of gangliosides in reception of influenza virus. Eur J Biochem 128:467–474, 1982.PubMedCrossRefGoogle Scholar
  12. 12.
    Carubia JM, Yu RK, Macala LJ, Kirkwood JM, Varga JM: Gangliosides of normal and neoplastic human melanocytes. Biochem Biophys Res Commun 120:500–504, 1984.PubMedCrossRefGoogle Scholar
  13. 13.
    Herlyn M, Rodeck U, Mancianti M, Cardillo FM, Land A, Ross AH, Jambrosic J, Koprowski H. Expression of melanoma-associated antigens in rapidly dividing human melanocytes in culture. Cancer Res 47:3057–3061, 1987.PubMedGoogle Scholar
  14. 14.
    Herrler G, Klenk H-D: The surface receptor is a major determinant of the cell tropism of Influenza C Virus. Virology 159:102–108, 1987.PubMedCrossRefGoogle Scholar
  15. 15.
    Dippold WG, Dienes HP, Knuth A, Meyer zum Buschenfelde K-H: Immunohistochemical localization of ganglioside GD3 in human malignant melanoma, epithelial tumors and normal tissues. Cancer Res 45:3699–3705, 1985.PubMedGoogle Scholar
  16. 16.
    Graus F, Cordon-Cardo C, Houghton AN, Melamed MR, Old, LJ: Distribution of the ganglioside GD3 in the human nervous system detected by R24 mouse monoclonal antibody. Brain Res 324:190–194, 1984.PubMedCrossRefGoogle Scholar
  17. 17.
    Portoukalian J, Zwingelstein G, Abdul-Malek N, Dore, J-F: Alteration of gangliosides in plasma and red cells of human bearing melanoma tumors. Biochem Biophys Res Commun 85:916–920, 1978.PubMedCrossRefGoogle Scholar
  18. 18.
    Pukel CS, Lloyd KO, Travassos LR, Dippold WG, Oettgen HF, Old LJ: GD3, a prominent ganglioside of human melanoma: Detection and characterization of mouse monoclonal antibody. J Exp Med 155:1133–1147, 1982.PubMedCrossRefGoogle Scholar
  19. 19.
    Muchmore EA, Varki NM, Fukuda M, Varki, A: Developmental regulation of sialic acid modifications in rat and human colon. FASEB J 1:229–235, 1987.PubMedGoogle Scholar
  20. 20.
    Cheresh DA, Reisfeld RA, Varki AP: O-acetylation of disialoganglioside GD3 by human melanoma cells creates a unique antigenic determinant. Science 225:844–846, 1984.PubMedCrossRefGoogle Scholar
  21. 21.
    Cheresh DA, Varki AP, Varki NM, Stallcup WB, Levine J, Reisfeld RA: A monoclonal antibody recognizes an O-acetyl sialic acid in a human melanoma-associated ganglioside. J Biol Chem 259:7453–7459, 1984.PubMedGoogle Scholar
  22. 22.
    Thurin J, Herlyn M, Hindsgaul O, Stromberg N, Karlsson K-A, Elder D, Steplewski Z, Koprowski H: Proton NMR and fast-atom bombardment mass spectrometry analysis of the melanoma-associated ganglioside 9-O-acetyl GD3. J Biol Chem 260:14556–14563, 1985.PubMedGoogle Scholar
  23. 23.
    Ravindranath MH, Paulson JC: O-acetyl sialic acid specific lectin from the crab Cancer antennarius. Methods Enzymol 138:520–527, 1987.PubMedCrossRefGoogle Scholar
  24. 24.
    Ravindranath MH, Paulson JC, Irie RF: Human melanoma antigen O-acetylated ganglioside GD3 is recognized by Cancer antennarius lectin. J Biol Chem 263:1–8, 1988.Google Scholar
  25. 25.
    Schroder C, Nohle U, Shukla AK, Schauer R: Improved methods for the isolation and structural analysis of trace amounts of new sialic acids—identification of N-glycolylneuraminic acid in man. In: Glycoconjugates, Proc. 12th Intl Symp, France, pp. 162–163, 1987.Google Scholar
  26. 26.
    Fuji Y, Higashi H, Ikuta K, Kato S, Naiki M: Specificities of human heterophilic Hanganutziu Deicher (H-D) antibodies and avian antisera against H-D antigen-active glycosphingolipids. Mol Immunol 19:87–94, 1982.CrossRefGoogle Scholar
  27. 27.
    Nakarai H, Saida T, Shibata Y, Irie RF, Kano K: Expression of heterophile, Paul-Bunnell and Hanganutziu-Deicher antigens on human melanoma cell lines. Int Archs Allergy Appl Immun 83:160–166, 1987.CrossRefGoogle Scholar
  28. 28.
    Hirabayashi Y, Higashi H, Kato S, Taniguchi M, Matsumoto M: Occurrence of tumor-associated ganglioside antigens with Hanganutziu-Deicher antigenic activity on human melanomas. Jpn J Cancer Res 78:614–620, 1987.PubMedGoogle Scholar
  29. 29.
    Herlyn M, Thurin J, Balaban G, Bennicelli JL, Herlyn D, Elder DE, Bondi E, Guerry D, Nowell P, Clark WH, Koprowski H: Characteristics of cultured human melanocytes isolated from different stages of tumor progression. Cancer Res 45:5670–5676, 1985.PubMedGoogle Scholar
  30. 30.
    Tsuchida T, Saxton RE, Irie RF: Gangliosides of human melanoma: GM2 and tumorigenicity. J Natl Cancer Inst 78:55–60, 1987.PubMedGoogle Scholar
  31. 31.
    Tsuchida T, Ravindranath MH, Saxton RE, Irie RF: Gangliosides of human melanoma: Altered expression in vivo and in vitro. Cancer Res 47:1278–1281, 1987.PubMedGoogle Scholar
  32. 32.
    Cahan LD, Irie RF, Singh R, Cassidenti A, Paulson JC: Identification of a human neuroectodermal tumor antigen (OFA-I-2) as ganglioside GD2. Proc Natl Acad Sci USA 79:7629–7633, 1982.PubMedCrossRefGoogle Scholar
  33. 33.
    Tai T, Paulson JC, Cahan CD, Irie RF. Ganglioside GM2 as a human tumor antigen (OFA-I-1). Proc Natl Acad Sci 80:5392–5396, 1983.PubMedCrossRefGoogle Scholar
  34. 34.
    Cheresh DA, Pierschbacher MD, Herzig MA, Mujoo K: Disialogangliosides GD2 and GD3 are involved in the attachment of human melanoma and neuroblastoma cells to extracellular matrix proteins. J Cell Biol 102:688–696, 1986.PubMedCrossRefGoogle Scholar
  35. 35.
    Cheresh DA, Klier FG: Disialoganglioside GD3 distributes preferentially into substrate associated microprocesses on human melanoma cells during their attachment to fibronectin. J Cell Biol 102:1887–1897, 1986.PubMedCrossRefGoogle Scholar
  36. 36.
    Herlyn M, Guerry D, Koprowski H: Recombinant gamma-interferon induces changes in expression and shedding of antigens associated with normal human melanocytes, nevues cells and primary and metastatic melanoma cells. J Immunol 134:4226–4229, 1985.PubMedGoogle Scholar
  37. 37.
    Keenan TW, Franke WW, Wiegandt H: Ganglioside accumulation by transformed murine fibroblasts (3T3) cells and canine erythrocytes. Hoppe-Seyler’s Z Physiol Chem 355:1543–1558, 1974.PubMedCrossRefGoogle Scholar
  38. 38.
    Rosenberg JM, Cheresh DA. Increased activity of cytidine-5′-monophospho-N-acetylneuraminic acid: GM3 sialyltransferase leads to the enhanced expression of GD3 on human melanoma cells derived from a metastatic lesion. Pros Am Soc Biol Chem 45:1822–1827, 1986.Google Scholar
  39. 39.
    Thurin J, Thurin M, Elder DE, Steplewski Z, Clark WH, Koprowski H: GD2 ganglioside biosynthesis is a distinct biochemical event in human melanoma tumor progression. FEBS Letters 208:17–22, 1986.PubMedCrossRefGoogle Scholar
  40. 40.
    Livingston PO, Natoli EJ, Calves MJ, Stockert E, Oettgen HF, Old LJ: Vaccines containing purified GM2 ganglioside elicit GM2 antibodies in melanoma patients. Proc Natl Acad Sci USA 84:2911–2915, 1987.PubMedCrossRefGoogle Scholar
  41. 41.
    Kono K, Tsuchida T, Ravindranath MH, Saxton RE, Irie RF: Gangliosides as tumor markers of human melanoma. (Submitted for publication 1987.Google Scholar
  42. 42.
    Nudelman E, Hakomori S, Kannagi R, Levery S, Yeh M-Y, Hellstrom KE, Hellstrom I: Characterization of a human melanoma-associated ganglioside antigen defined by a monoclonal antibody 4.2. J Biol Chem 257:12752–12756, 1982.PubMedGoogle Scholar
  43. 43.
    Brodin T, Hellstrom I, Hellstrom KE, Karlsson K-A, Sjogren H-O, Stromberg N, Thurin J. Mouse monoclonal antibodies with specificity for the melanoma-associated ganglioside disialyllactosyl ceramide (GD3) also react with the structural analogue disialylparaglobo-side. Biochim Biophys Acta 837:349–353, 1985.PubMedGoogle Scholar
  44. 44.
    Marcus DM: A review of the immunogenic and immunomodulatory properties of glycosphingolipids. Mol Immunol 21:1083–1091, 1984.PubMedCrossRefGoogle Scholar
  45. 45.
    Yeh M-Y, Hellstrom I, Abe K, Hakomori S, Hellstrom KE: A cell-surface antigen which is present in the ganglioside fraction and shared by human melanomas. Int J Cancer 29:269–275, 1982.PubMedCrossRefGoogle Scholar
  46. 46.
    Hellstrom I, Brankovan V, Hellstrom KE: Strong anti-tumor activities of IgG 3 antibodies to a human melanoma-associated ganglioside. Proc Natl Acad Sci USA 82:1499–1502, 1985.PubMedCrossRefGoogle Scholar
  47. 47.
    Cheresh DA, Honsik CJ, Staffileno LK, Jung G, Reisfeld RA: Disialoganglioside GD3 on human melanoma serves as a relevant target antigen for monoclonal antibody-mediated tumor cytolysis. Proc Natl Acad Sci USA 82:5155–5159, 1985.PubMedCrossRefGoogle Scholar
  48. 48.
    Cheresh DA, Harper JR, Schulz G, Reisfeld RA: Localization of gangliosides GD2 and GD3 in adhesion plaques and on the surface of human melanoma cells. Proc Natl Acad Sci USA 81:5767–5771, 1984.PubMedCrossRefGoogle Scholar
  49. 49.
    Kundu SK, Samuelsson BE, Pascher I, Marcus DM: New gangliosides from human erythrocytes. J Biol Chem 258:13857–13866, 1983.PubMedGoogle Scholar
  50. 50.
    Rauvala H: Gangliosides of human kidney. J Biol Chem 251:7517–7520, 1976.PubMedGoogle Scholar
  51. 51.
    Cheung NV, Vol Hoff DD, Strandjord, Coccia PF: Detection of neuroblastoma cells in bone marrow using GD2 specific monoclonal antibodies. J Clin Oncol 4:363–369, 1986.PubMedGoogle Scholar
  52. 52.
    Natoli EJ Jr, Livingston PO, Pukel CS, Lloyd KO, Wiegandt H, Szalay J, Oettgen HF, Old LJ: A murine monoclonal antibody detecting the ganglioside GM2: Characterization of cell surface reactivity. Cancer Res (in press), 1987.Google Scholar
  53. 53.
    Hirabayashi Y, Sugimoto M, Ogawa T, Matsumoto M, Tagawa M, Taniguchi M: Reactivity of mouse monoclonal antibody M2590 against B16 melanoma cells with chemically sythesized GM3 ganglioside. Biochim Biophys Acta 875:126–128, 1986.PubMedGoogle Scholar
  54. 54.
    Irie RF, Sze LL, Saxton RE: Human antibody to OFA-I, a tumor antigen, produced in vitro by Epstein-Barr virus transformed human B-lymphoid cell lines. Proc Natl Acad Sci USA 79:5666–5670, 1982.PubMedCrossRefGoogle Scholar
  55. 55.
    Katano M, Saxton RE, Irie RF: Human monoclonal antibody to tumor-associated ganglioside GD2. J Clin Lab Immunol 15:119–126, 1984.PubMedGoogle Scholar
  56. 56.
    Yamaguchi H, Furukawa K, Fortunato SR, Livingston PO, Lloyd KO, Oettgen HR, Old LJ: Cell-surface antigens of melanoma recognized by human monoclonal antibodies. Proc Natl Acad Sci USA 84:2416–2420, 1987.PubMedCrossRefGoogle Scholar
  57. 57.
    Ladisch S, Wu Z-L, Feig S, Ulsh L, Schwartz E, Floutsis G, Wiley F, Lenarsky C, Seeger R: Shedding of GD2 ganglioside by human neuroblastoma. Int J Cancer 39:73–76, 1987.PubMedCrossRefGoogle Scholar
  58. 58.
    Portoukalian J, Zwingelstein G, Dore J-F, Bourgoin J-J: Studies of a ganglioside fraction extracted from human malignant melanoma. Biochimie 58:1285–1287, 1976.PubMedCrossRefGoogle Scholar
  59. 59.
    Watanabe T, Pukel CS, Takeyama H, Lloyd KO, Shiku H, Li LTC, Travassos LR, Oettigen HF, Old LJ: Human melanoma antigen AH is an autoantigenic ganglioside related to GD2. J Exp Med 156:1884–1889, 1983.CrossRefGoogle Scholar
  60. 60.
    Tai T, Cahan LD, Tsuchida T, Morton DL, Irie RF: Immunogenicity of melanoma-associated gangliosides in cancer patients. Int J Cancer 35:607–612, 1985.PubMedCrossRefGoogle Scholar
  61. 61.
    Hakansson L, Fredman P, Svennerholm L: Gangliosides in serum immune complexes from tumor-bearing patients. J Biochem 98:843–849, 1985.PubMedGoogle Scholar
  62. 62.
    Morton DL, Nizze JA, Gupta RK, Famatiga E, Hoon DSB, Irie RF: Active specific immunotherapy of malignant melanoma. In: Current status of cancer control and therapy, Kim JP, Kim BS, Park J-G (eds. and pub.), pp. 152–161, 1987.Google Scholar
  63. 63.
    Irie RF, Giullano AE, Morton DL: Oncofetal antigen: A tumor-associated fetal antigen immunogenic in man. J Natl Cancer Inst 63:367–373, 1979.PubMedGoogle Scholar
  64. 64.
    Irie K, Irie RF, Morton DL: Humoral immune response to melanoma associated membrane antigen and fetal brain antigen demonstrated by indirect membrane immunofluorescence I. Can Immunol Immunother 6:33–39, 1979.Google Scholar
  65. 65.
    Dippold W, Knuth A, Meyer zum Buschenfelde K-H: Inflammatory response at the tumor site after systemic application of monoclonal anti-GD3-ganglioside antibody to patients with malignant melanoma. Am Assoc Cancer Res 978:247, 1984.Google Scholar
  66. 66.
    Houghton AN, Mintzer D, Cordon-Cardo C, Welt S, Fliegel B, Vadhan S, Carswell E, Melamed MR, Oettgen HF, Old LJ: Mouse monoclonal IgG3 antibody detecting GD3 ganglioside: A phase I trial in patients with malignant melanoma. Proc Natl Acad Sci USA 82:1242–1246, 1985.PubMedCrossRefGoogle Scholar
  67. 67.
    Cheung NV, Lazarus H, Miraldi FD, Abramowsky CR, Kallick S, Saarinen UM, Spitzer T, Strandjord SE, Coccia PF, and Berger NA: Ganglioside GD2 specific monoclonal antibody 3F8: A phase I study in patients with neuroblastoma and malignant melanoma. J Clin Oncol 5:1430–1440, 1987.PubMedGoogle Scholar
  68. 68.
    Bajorin D, Chapman P, Kunicka J, Cordon-Cardo C, Welt K, Mertelsmann R, Melamed M, Oettgen HF, Old LJ, Houghton AH: Phase I trial of a combination of R24 mouse monoclonal antibody and recombinant interleukin-2 in patients with melanoma. Amer Assoc Cancer Res 827:210, 1987.Google Scholar
  69. 69.
    Lichtin AE, Guerry D, Elder DE, Hamilton R, LaRossa D, Herlyn D, Iliopoulos D, Thurin J, Steplewski Z: A phase I study of monoclonal antibody therapy in disseminated melanoma. Proc 8th Interntl Pigment Cell Confer, Tucson, Alizona, 1986,Google Scholar
  70. 70.
    Goodman GE, Hellstrom I, Hummel D, Brodzinsky L, Yeh MY, Hellstrom KE: Phase I trial of monoclonal antibody MG-21 directed against a melanoma associated GD3 ganglioside antigen. Proc Am Soc Clin Oncol 6:A823, 1987.Google Scholar
  71. 71.
    Ankel H, Krishnamurthi C, Besancon F, Stefano S, Falcoff E: Mouse fibroblast (type I) and immune (type II) interferons: Pronounces differences in affinity for gangliosides and in antiviral and antigrowth effects on mouse leukemia L-1210R cells. Proc Natl Acad Sci USA 77:2528–2532, 1980.PubMedCrossRefGoogle Scholar
  72. 72.
    MacDonald HS, Elconin H, Ankel H: Leukemic cells sensitive or resistant to beta-interferon have identical ganglioside patterns. FEBS letters 141:267–270, 1982.PubMedCrossRefGoogle Scholar
  73. 73.
    Hoon DSB, Irie RF, Cochran AJ: Gangliosides from human melanoma immunomodulate response of T-cells to interleukin-2. Cell Immunol 111:1–10, 1988.CrossRefGoogle Scholar
  74. 74.
    Ando I, Hoon DSB, Suzuki Y, Saxton RE, Golub SH, Irie RF: Ganglioside GM2 on the K562 cell line is recognized as a target structure by human natural killer cells. Int J Cancer 40:12–17, 1987.PubMedCrossRefGoogle Scholar
  75. 75.
    Ando I, Hoon DB, Pattengale PK, Golub SH, Irie RF: Ganglioside GM2 as a target structure recognized by human natural killer cells. J Clin Lab Anal 1:209–213, 1987.CrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers, Boston 1988

Authors and Affiliations

  • Mepur H. Ravindranath
  • Reiko F. Irie

There are no affiliations available

Personalised recommendations