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Am J Pathol. Jun 1997; 150(6): 2143–2152.
PMCID: PMC1858329

Molecular detection of tumor-associated antigens shared by human cutaneous melanomas and gliomas.

Abstract

Both melanocytes and glial cells are derived embryologically from the neural ectoderm. Their malignant transformed counterparts, melanoma and glioma cells, respectively, may share common antigens. Numerous tumor-associated antigens have been identified in melanomas but only a few a gliomas. Using an established reverse transcriptase polymerase chain reaction plus Southern blot assay, we compared the mRNA expression of melanoma-associated antigens (MAAs) of melanomas to brain tumors primarily derived from glial cells. The MAAs studied included tyrosinase (Tyr), tyrosinase-related protein-1 and -2 (TRP-1 and TRP-2), gp100, human melanoma antigen-encoding genes 1 and 3 (MAGE-1 and MAGE-3), and melanotransferrin (p97). Glioblastoma multiforme (n = 21), anaplastic astrocytoma (n = 3), ependymoma (n = 2), meningioma (n = 3), oligodendroglioma (n = 1), and melanoma (n = 12) tumor specimens were assayed for MAA mRNA expression. Glioblastoma multiforme, astrocytoma, and melanoma cell lines were also assayed. We observed that individual MAA mRNAs were expressed in these brain tumors and cell lines at varying frequencies. The melanogenesis-pathway-related MAAs Tyr, TRP-1, TRP-2, and gp100 mRNAs were also expressed at different levels in normal brain tissues but at a much lower frequency than in glioblastoma multiforme and melanoma. MAGE-1 and MAGE-3 mRNA were expressed in different types of tumor specimens and cell lines but never in normal brain tissue. Tumor antigen p97 was expressed in all types of tumors and also in normal brain tissues. These studies demonstrate that melanomas and primary brain tumors express common MAAs and could be exploited in patients with malignant glioma by active specific immunotherapy against these common MAAs.

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Selected References

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  • Lallier TE. Cell lineage and cell migration in the neural crest. Ann N Y Acad Sci. 1991;615:158–171. [PubMed]
  • Rimoldi D, Romero P, Carrel S. The human melanoma antigen-encoding gene, MAGE-1, is expressed by other tumour cells of neuroectodermal origin such as glioblastomas and neuroblastomas. Int J Cancer. 1993 May 28;54(3):527–528. [PubMed]
  • Seeger RC, Rosenblatt HM, Imai K, Ferrone S. Common antigenic determinants on human melanoma, glioma, neuroblastoma, and sarcoma cells defined with monoclonal antibodies. Cancer Res. 1981 Jul;41(7):2714–2717. [PubMed]
  • Wikstrand CJ, Bigner DD. Expression of human fetal brain antigens by human tumors of neuroectodermal origin as defined by monoclonal antibodies. Cancer Res. 1982 Jan;42(1):267–275. [PubMed]
  • Azizi E, Friedman J, Pavlotsky F, Iscovich J, Bornstein A, Shafir R, Trau H, Brenner H, Nass D. Familial cutaneous malignant melanoma and tumors of the nervous system. A hereditary cancer syndrome. Cancer. 1995 Nov 1;76(9):1571–1578. [PubMed]
  • Soffer D, Lach B, Constantini S. Melanotic cerebral ganglioglioma: evidence for melanogenesis in neoplastic astrocytes. Acta Neuropathol. 1992;83(3):315–323. [PubMed]
  • Haninec P, Vachtenheim J. Tyrosinase protein is expressed also in some neural crest derived cells which are not melanocytes. Pigment Cell Res. 1988;1(5):340–343. [PubMed]
  • McCloskey JJ, Parker JC, Jr, Brooks WH, Blacker HM. Melanin as a component of cerebral gliomas: the melanotic cerebral ependymoma. Cancer. 1976 May;37(5):2373–2379. [PubMed]
  • Spagnoli GC, Schaefer C, Willimann TE, Kocher T, Amoroso A, Juretic A, Zuber M, Luscher U, Harder F, Heberer M. Peptide-specific CTL in tumor infiltrating lymphocytes from metastatic melanomas expressing MART-1/Melan-A, gp100 and Tyrosinase genes: a study in an unselected group of HLA-A2.1-positive patients. Int J Cancer. 1995 Oct 20;64(5):309–315. [PubMed]
  • Hoon DS, Yuzuki D, Hayashida M, Morton DL. Melanoma patients immunized with melanoma cell vaccine induce antibody responses to recombinant MAGE-1 antigen. J Immunol. 1995 Jan 15;154(2):730–737. [PubMed]
  • Gaugler B, Van den Eynde B, van der Bruggen P, Romero P, Gaforio JJ, De Plaen E, Lethé B, Brasseur F, Boon T. Human gene MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes. J Exp Med. 1994 Mar 1;179(3):921–930. [PMC free article] [PubMed]
  • van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science. 1991 Dec 13;254(5038):1643–1647. [PubMed]
  • Song YH, Connor E, Li Y, Zorovich B, Balducci P, Maclaren N. The role of tyrosinase in autoimmune vitiligo. Lancet. 1994 Oct 15;344(8929):1049–1052. [PubMed]
  • Morton DL, Foshag LJ, Hoon DS, Nizze JA, Famatiga E, Wanek LA, Chang C, Davtyan DG, Gupta RK, Elashoff R, et al. Prolongation of survival in metastatic melanoma after active specific immunotherapy with a new polyvalent melanoma vaccine. Ann Surg. 1992 Oct;216(4):463–482. [PMC free article] [PubMed]
  • Barth A, Hoon DS, Foshag LJ, Nizze JA, Famatiga E, Okun E, Morton DL. Polyvalent melanoma cell vaccine induces delayed-type hypersensitivity and in vitro cellular immune response. Cancer Res. 1994 Jul 1;54(13):3342–3345. [PubMed]
  • Hoon DS, Wang Y, Dale PS, Conrad AJ, Schmid P, Garrison D, Kuo C, Foshag LJ, Nizze AJ, Morton DL. Detection of occult melanoma cells in blood with a multiple-marker polymerase chain reaction assay. J Clin Oncol. 1995 Aug;13(8):2109–2116. [PubMed]
  • Doi F, Chi DD, Charuworn BB, Conrad AJ, Russell J, Morton DL, Hoon DS. Detection of beta-human chorionic gonadotropin mRNA as a marker for cutaneous malignant melanoma. Int J Cancer. 1996 Feb 8;65(4):454–459. [PubMed]
  • Hoon DS, Sarantou T, Doi F, Chi DD, Kuo C, Conrad AJ, Schmid P, Turner R, Guiliano A. Detection of metastatic breast cancer by beta-hCG polymerase chain reaction. Int J Cancer. 1996 Oct 21;69(5):369–374. [PubMed]
  • Datta YH, Adams PT, Drobyski WR, Ethier SP, Terry VH, Roth MS. Sensitive detection of occult breast cancer by the reverse-transcriptase polymerase chain reaction. J Clin Oncol. 1994 Mar;12(3):475–482. [PubMed]
  • Anker L, Ohgaki H, Ludeke BI, Herrmann HD, Kleihues P, Westphal M. p53 protein accumulation and gene mutations in human glioma cell lines. Int J Cancer. 1993 Dec 2;55(6):982–987. [PubMed]
  • Tsuzuki T, Tsunoda S, Sakaki T, Konishi N, Hiasa Y, Nakamura M. Alterations of retinoblastoma, p53, p16(CDKN2), and p15 genes in human astrocytomas. Cancer. 1996 Jul 15;78(2):287–293. [PubMed]
  • Ritland SR, Ganju V, Jenkins RB. Region-specific loss of heterozygosity on chromosome 19 is related to the morphologic type of human glioma. Genes Chromosomes Cancer. 1995 Apr;12(4):277–282. [PubMed]
  • Nordlund JJ, Abdel-Malek ZA, Boissy RE, Rheins LA. Pigment cell biology: an historical review. J Invest Dermatol. 1989 Apr;92(4 Suppl):53S–60S. [PubMed]
  • Kwon BS, Haq AK, Pomerantz SH, Halaban R. Isolation and sequence of a cDNA clone for human tyrosinase that maps at the mouse c-albino locus. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7473–7477. [PMC free article] [PubMed]
  • del Marmol V, Beermann F. Tyrosinase and related proteins in mammalian pigmentation. FEBS Lett. 1996 Mar 4;381(3):165–168. [PubMed]
  • Vijayasaradhi S, Bouchard B, Houghton AN. The melanoma antigen gp75 is the human homologue of the mouse b (brown) locus gene product. J Exp Med. 1990 Apr 1;171(4):1375–1380. [PMC free article] [PubMed]
  • Jackson IJ, Chambers DM, Tsukamoto K, Copeland NG, Gilbert DJ, Jenkins NA, Hearing V. A second tyrosinase-related protein, TRP-2, maps to and is mutated at the mouse slaty locus. EMBO J. 1992 Feb;11(2):527–535. [PMC free article] [PubMed]
  • Kwon BS, Chintamaneni C, Kozak CA, Copeland NG, Gilbert DJ, Jenkins N, Barton D, Francke U, Kobayashi Y, Kim KK. A melanocyte-specific gene, Pmel 17, maps near the silver coat color locus on mouse chromosome 10 and is in a syntenic region on human chromosome 12. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9228–9232. [PMC free article] [PubMed]
  • Kwon BS. Pigmentation genes: the tyrosinase gene family and the pmel 17 gene family. J Invest Dermatol. 1993 Feb;100(2 Suppl):134S–140S. [PubMed]
  • Russo V, Traversari C, Verrecchia A, Mottolese M, Natali PG, Bordignon C. Expression of the MAGE gene family in primary and metastatic human breast cancer: implications for tumor antigen-specific immunotherapy. Int J Cancer. 1995 Jun 22;64(3):216–221. [PubMed]
  • Weynants P, Lethé B, Brasseur F, Marchand M, Boon T. Expression of mage genes by non-small-cell lung carcinomas. Int J Cancer. 1994 Mar 15;56(6):826–829. [PubMed]
  • Woodbury RG, Brown JP, Yeh MY, Hellström I, Hellström KE. Identification of a cell surface protein, p97, in human melanomas and certain other neoplasms. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2183–2187. [PMC free article] [PubMed]
  • Brown JP, Woodbury RG, Hart CE, Hellström I, Hellström KE. Quantitative analysis of melanoma-associated antigen p97 in normal and neoplastic tissues. Proc Natl Acad Sci U S A. 1981 Jan;78(1):539–543. [PMC free article] [PubMed]
  • Hoon DS, Ando I, Sviland G, Tsuchida T, Okun E, Morton DL, Irie RF. Ganglioside GM2 expression on human melanoma cells correlates with sensitivity to lymphokine-activated killer cells. Int J Cancer. 1989 May 15;43(5):857–862. [PubMed]
  • Mitchell MS, Harel W, Kan-Mitchell J, LeMay LG, Goedegebuure P, Huang XQ, Hofman F, Groshen S. Active specific immunotherapy of melanoma with allogeneic cell lysates. Rationale, results, and possible mechanisms of action. Ann N Y Acad Sci. 1993 Aug 12;690:153–166. [PubMed]
  • Maeurer MJ, Storkus WJ, Kirkwood JM, Lotze MT. New treatment options for patients with melanoma: review of melanoma-derived T-cell epitope-based peptide vaccines. Melanoma Res. 1996 Feb;6(1):11–24. [PubMed]
  • Sawamura Y, De Tribolet N. Immunotherapy of brain tumors. J Neurosurg Sci. 1990 Jul-Dec;34(3-4):265–278. [PubMed]
  • Madajewicz S, Karakousis C, West CR, Caracandas J, Avellanosa AM. Malignant melanoma brain metastases. Review of Roswell Park Memorial Institute experience. Cancer. 1984 Jun 1;53(11):2550–2552. [PubMed]
  • Rabey JM, Hefti F. Neuromelanin synthesis in rat and human substantia nigra. J Neural Transm Park Dis Dement Sect. 1990;2(1):1–14. [PubMed]
  • Cowen D. The melanoneurons of the human cerebellum (nucleus pigmentosus cerebellaris) and homologues in the monkey. J Neuropathol Exp Neurol. 1986 May;45(3):205–221. [PubMed]
  • Lampson LA, Hickey WF. Monoclonal antibody analysis of MHC expression in human brain biopsies: tissue ranging from "histologically normal" to that showing different levels of glial tumor involvement. J Immunol. 1986 Jun 1;136(11):4054–4062. [PubMed]
  • Natali PG, Bigotti A, Nicotra MR, Viora M, Manfredi D, Ferrone S. Distribution of human Class I (HLA-A,B,C) histocompatibility antigens in normal and malignant tissues of nonlymphoid origin. Cancer Res. 1984 Oct;44(10):4679–4687. [PubMed]

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