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. 1989 Feb;134(2):295–303.

Cell surface molecules of human melanoma. Immunohistochemical analysis of the gp57, GD3, and mel-CSPG antigenic systems.

P Garin-Chesa 1, H R Beresford 1, A Carrato-Mena 1, H F Oettgen 1, L J Old 1, M R Melamed 1, W J Rettig 1
PMCID: PMC1879571  PMID: 2916650

Abstract

The rapidly expanding list of monoclonal antibodies (MAbs) to human cell surface antigens provides reagents to probe the biology of malignant melanoma and to develop new diagnostic and therapeutic approaches to this disease. The criteria used to select MAb-defined antigens as targets for passive immunotherapy or immunolocalization of melanoma include: 1) consistent antigen expression in melanomas, 2) restricted antigen distribution in normal tissues and nonmelanocytic tumors, and 3) cytotoxic activity of the MAb or MAb conjugates. The present study examined the tissue distribution of three prototype melanoma cell surface antigens, the Mr 57,000 glycoprotein (gp57) recognized by MAb A42, the GD3 ganglioside, and the mel-CSPG chondroitin sulfate proteoglycan. The avidin-biotin immunoperoxidase method was used to examine a large panel of normal tissues and over 150 malignant tumors. It was found that A42 has a highly restricted distribution in normal tissues and is expressed in subsets of melanomas and nonmelanocytic tumors. It was also found that GD3 and mel-CSPG are more widely distributed in normal tissues and among tumors than was thought previously. These immunohistochemical patterns provide an essential data base to evaluate the ongoing clinical trials employing MAbs to GD3 and mel-CSPG for the therapy and immunolocalization of melanomas, and they identify gp57 as a potential marker for subsets of normal and transformed melanocytic cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bumol T. F., Walker L. E., Reisfeld R. A. Biosynthetic studies of proteoglycans in human melanoma cells with a monoclonal antibody to a core glycoprotein of chondroitin sulfate proteoglycans. J Biol Chem. 1984 Oct 25;259(20):12733–12741. [PubMed] [Google Scholar]
  2. Cairncross J. G., Mattes M. J., Beresford H. R., Albino A. P., Houghton A. N., Lloyd K. O., Old L. J. Cell surface antigens of human astrocytoma defined by mouse monoclonal antibodies: identification of astrocytoma subsets. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5641–5645. doi: 10.1073/pnas.79.18.5641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carrel S., Accolla R. S., Carmagnola A. L., Mach J. P. Common human melanoma-associated antigen(s) detected by monoclonal antibodies. Cancer Res. 1980 Jul;40(7):2523–2528. [PubMed] [Google Scholar]
  4. Chesa P. G., Rettig W. J., Melamed M. R. Expression of cytokeratins in normal and neoplastic colonic epithelial cells. Implications for cellular differentiation and carcinogenesis. Am J Surg Pathol. 1986 Dec;10(12):829–835. doi: 10.1097/00000478-198612000-00001. [DOI] [PubMed] [Google Scholar]
  5. Chesa P. G., Rettig W. J., Melamed M. R., Old L. J., Niman H. L. Expression of p21ras in normal and malignant human tissues: lack of association with proliferation and malignancy. Proc Natl Acad Sci U S A. 1987 May;84(10):3234–3238. doi: 10.1073/pnas.84.10.3234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dippold W. G., Dienes H. P., Knuth A., Meyer zum Büschenfelde K. H. Immunohistochemical localization of ganglioside GD3 in human malignant melanoma, epithelial tumors, and normal tissues. Cancer Res. 1985 Aug;45(8):3699–3705. [PubMed] [Google Scholar]
  7. Dippold W. G., Lloyd K. O., Li L. T., Ikeda H., Oettgen H. F., Old L. J. Cell surface antigens of human malignant melanoma: definition of six antigenic systems with mouse monoclonal antibodies. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6114–6118. doi: 10.1073/pnas.77.10.6114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gordon J. W., Chesa P. G., Nishimura H., Rettig W. J., Maccari J. E., Endo T., Seravalli E., Seki T., Silver J. Regulation of Thy-1 gene expression in transgenic mice. Cell. 1987 Jul 31;50(3):445–452. doi: 10.1016/0092-8674(87)90498-3. [DOI] [PubMed] [Google Scholar]
  9. Herlyn M., Clark W. H., Rodeck U., Mancianti M. L., Jambrosic J., Koprowski H. Biology of tumor progression in human melanocytes. Lab Invest. 1987 May;56(5):461–474. [PubMed] [Google Scholar]
  10. Hersey P., Schibeci S. D., Townsend P., Burns C., Cheresh D. A. Potentiation of lymphocyte responses by monoclonal antibodies to the ganglioside GD3. Cancer Res. 1986 Dec;46(12 Pt 1):6083–6090. [PubMed] [Google Scholar]
  11. Houghton A. N., Eisinger M., Albino A. P., Cairncross J. G., Old L. J. Surface antigens of melanocytes and melanomas. Markers of melanocyte differentiation and melanoma subsets. J Exp Med. 1982 Dec 1;156(6):1755–1766. doi: 10.1084/jem.156.6.1755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Houghton A. N., Mintzer D., Cordon-Cardo C., Welt S., Fliegel B., Vadhan S., Carswell E., Melamed M. R., Oettgen H. F., Old L. J. Mouse monoclonal IgG3 antibody detecting GD3 ganglioside: a phase I trial in patients with malignant melanoma. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1242–1246. doi: 10.1073/pnas.82.4.1242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kantor R. R., Ng A. K., Giacomini P., Ferrone S. Analysis of the NIH workshop monoclonal antibodies to human melanoma antigens. Hybridoma. 1982;1(4):473–482. doi: 10.1089/hyb.1.1982.1.473. [DOI] [PubMed] [Google Scholar]
  14. Ledbetter J. A., Rouse R. V., Micklem H. S., Herzenberg L. A. T cell subsets defined by expression of Lyt-1,2,3 and Thy-1 antigens. Two-parameter immunofluorescence and cytotoxicity analysis with monoclonal antibodies modifies current views. J Exp Med. 1980 Aug 1;152(2):280–295. doi: 10.1084/jem.152.2.280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Liotta L. A. Tumor invasion and metastases--role of the extracellular matrix: Rhoads Memorial Award lecture. Cancer Res. 1986 Jan;46(1):1–7. [PubMed] [Google Scholar]
  16. Morgan A. C., Jr, Galloway D. R., Reisfeld R. A. Production and characterization of monoclonal antibody to a melanoma specific glycoprotein. Hybridoma. 1981;1(1):27–36. doi: 10.1089/hyb.1.1981.1.27. [DOI] [PubMed] [Google Scholar]
  17. Natali P. G., Cavaliere R., Bigotti A., Nicotra M. R., Russo C., Ng A. K., Giacomini P., Ferrone S. Antigenic heterogeneity of surgically removed primary and autologous metastatic human melanoma lesions. J Immunol. 1983 Mar;130(3):1462–1466. [PubMed] [Google Scholar]
  18. Nudelman E., Hakomori S., Kannagi R., Levery S., Yeh M. Y., Hellström K. E., Hellström I. Characterization of a human melanoma-associated ganglioside antigen defined by a monoclonal antibody, 4.2. J Biol Chem. 1982 Nov 10;257(21):12752–12756. [PubMed] [Google Scholar]
  19. Oldham R. K., Foon K. A., Morgan A. C., Woodhouse C. S., Schroff R. W., Abrams P. G., Fer M., Schoenberger C. S., Farrell M., Kimball E. Monoclonal antibody therapy of malignant melanoma: in vivo localization in cutaneous metastasis after intravenous administration. J Clin Oncol. 1984 Nov;2(11):1235–1244. doi: 10.1200/JCO.1984.2.11.1235. [DOI] [PubMed] [Google Scholar]
  20. Pukel C. S., Lloyd K. O., Travassos L. R., Dippold W. G., Oettgen H. F., Old L. J. GD3, a prominent ganglioside of human melanoma. Detection and characterisation by mouse monoclonal antibody. J Exp Med. 1982 Apr 1;155(4):1133–1147. doi: 10.1084/jem.155.4.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Real F. X., Houghton A. N., Albino A. P., Cordon-Cardo C., Melamed M. R., Oettgen H. F., Old L. J. Surface antigens of melanomas and melanocytes defined by mouse monoclonal antibodies: specificity analysis and comparison of antigen expression in cultured cells and tissues. Cancer Res. 1985 Sep;45(9):4401–4411. [PubMed] [Google Scholar]
  22. Real F. X., Rettig W. J., Chesa P. G., Melamed M. R., Old L. J., Mendelsohn J. Expression of epidermal growth factor receptor in human cultured cells and tissues: relationship to cell lineage and stage of differentiation. Cancer Res. 1986 Sep;46(9):4726–4731. [PubMed] [Google Scholar]
  23. Rettig W. J., Chesa P. G., Jennings M. T., Spengler B. A., Melamed M. R., Oettgen H. F., Biedler J. L., Old L. J. Cell surface antigen of human neuroblastomas is related to nuclear antigen of normal cells. Proc Natl Acad Sci U S A. 1985 Oct;82(20):6894–6898. doi: 10.1073/pnas.82.20.6894. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rettig W. J., Garin-Chesa P., Beresford H. R., Oettgen H. F., Melamed M. R., Old L. J. Cell-surface glycoproteins of human sarcomas: differential expression in normal and malignant tissues and cultured cells. Proc Natl Acad Sci U S A. 1988 May;85(9):3110–3114. doi: 10.1073/pnas.85.9.3110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rettig W. J., Grzeschik K. H., Yenamandra A. K., Garcia E., Old L. J. Definition of selectable cell surface markers for human chromosomes and chromosome segments in rodent-human hybrids. Somat Cell Mol Genet. 1988 May;14(3):223–231. doi: 10.1007/BF01534583. [DOI] [PubMed] [Google Scholar]
  26. Rettig W. J., Murty V. V., Mattes M. J., Chaganti R. S., Old L. J. Extracellular matrix-modulated expression of human cell surface glycoproteins A42 and J143. Intrinsic and extrinsic signals determine antigenic phenotype. J Exp Med. 1986 Nov 1;164(5):1581–1599. doi: 10.1084/jem.164.5.1581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rettig W. J., Real F. X., Spengler B. A., Biedler J. L., Old L. J. Human melanoma proteoglycan: expression in hybrids controlled by intrinsic and extrinsic signals. Science. 1986 Mar 14;231(4743):1281–1284. doi: 10.1126/science.3633135. [DOI] [PubMed] [Google Scholar]
  28. Rettig W. J., Spengler B. A., Chesa P. G., Old L. J., Biedler J. L. Coordinate changes in neuronal phenotype and surface antigen expression in human neuroblastoma cell variants. Cancer Res. 1987 Mar 1;47(5):1383–1389. [PubMed] [Google Scholar]
  29. Ross A. H., Cossu G., Herlyn M., Bell J. R., Steplewski Z., Koprowski H. Isolation and chemical characterization of a melanoma-associated proteoglycan antigen. Arch Biochem Biophys. 1983 Aug;225(1):370–383. doi: 10.1016/0003-9861(83)90042-5. [DOI] [PubMed] [Google Scholar]
  30. Siccardi A. G., Buraggi G. L., Callegaro L., Mariani G., Natali P. G., Abbati A., Bestagno M., Caputo V., Mansi L., Masi R. Multicenter study of immunoscintigraphy with radiolabeled monoclonal antibodies in patients with melanoma. Cancer Res. 1986 Sep;46(9):4817–4822. [PubMed] [Google Scholar]
  31. Wilson B. S., Imai K., Natali P. G., Ferrone S. Distribution and molecular characterization of a cell-surface and a cytoplasmic antigen detectable in human melanoma cells with monoclonal antibodies. Int J Cancer. 1981 Sep 15;28(3):293–300. doi: 10.1002/ijc.2910280307. [DOI] [PubMed] [Google Scholar]
  32. Yeh M. Y., Hellström I., Abe K., Hakomori S., Hellström K. E. A cell-surface antigen which is present in the ganglioside fraction and shared by human melanomas. Int J Cancer. 1982 Mar 15;29(3):269–275. doi: 10.1002/ijc.2910290308. [DOI] [PubMed] [Google Scholar]
  33. Ziai M. R., Imberti L., Nicotra M. R., Badaracco G., Segatto O., Natali P. G., Ferrone S. Analysis with monoclonal antibodies of the molecular and cellular heterogeneity of human high molecular weight melanoma associated antigen. Cancer Res. 1987 May 1;47(9):2474–2480. [PubMed] [Google Scholar]

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