Abstract
Clones were isolated from the cultured human melanoma cell line MeM 50-10, which metastasizes in nude mice with a pattern similar to that in patients with melanoma. Analysis with monoclonal antibodies detected heterogeneity among the clones in the expression of HLA class I antigens, HLA class II antigens, intercellular adhesion molecule 1 and high molecular weight melanoma associated antigen. The clones MeM A16 and MeM A18 were also shown to display differential susceptibility to modulation by immune interferon (IFN-γ) and/or tumor necrosis factor (TNF-α) of the expression of the four types of antigens analyzed. In spite of differences in the antigenic profile, the two clones did not differ in their susceptibility to lysis by lymphokine-activated killer (LAK) cells and by anti-HLA-A2 cytotoxic T cells. The increase in the expression of HLA class I antigens induced by IFN-γ and/or TNF-α on the two clones was associated with an increased susceptibility to lysis by anti-HLA-A2 cytotoxic T cells. Because of the metastasizing properties of cultured melanoma cells MeM 50-10, the clones we have isolated, with their distinct antigenic profile and differential susceptibility to modulation by cytokines, may represent useful models to investigate the role of distinct antigenic structures in the metastatic process.
Keywords: Melanoma, Melanoma Cell, Human Melanoma, Antigen Expression, Intercellular Adhesion Molecule
Footnotes
This work was supported by the National Institutes of Health grants AI21384, CA37959 and CA39559
References
- 1.Albino AP, Lloyd KO, Houghton AN, Oettgen HF, Old LJ. Heterogeneity in surface antigen and glycoprotein expression of cell lines derived from different melanoma metastases of the same patient. J Exp Med. 1981;154:1764. doi: 10.1084/jem.154.6.1764. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Anichini A, Fossati G, Parmiani G. Heterogeneity of clones from a human metastatic melanoma detected by autologous cytotoxic T lymphocyte clones. J Exp Med. 1986;163:215. doi: 10.1084/jem.163.1.215. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Anichini A, Mortarini R, Fossati G, Parmiani G. Phenotypic profile of clones from early cultures of human metastatic melanomas and its modulation by recombinant interferon γ. Int J Cancer. 1986;38:505. doi: 10.1002/ijc.2910380409. [DOI] [PubMed] [Google Scholar]
- 4.Barnstable CJ, Bodmer WF, Brown G, Galfre G, Milstein C, Williams AF, Ziegler A. Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-New tools for genetic analysis. Cell. 1978;14:9. doi: 10.1016/0092-8674(78)90296-9. [DOI] [PubMed] [Google Scholar]
- 5.Bonner WM, Laskey RA. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamidegels. Eur J Biochem. 1974;46:83. doi: 10.1111/j.1432-1033.1974.tb03599.x. [DOI] [PubMed] [Google Scholar]
- 6.Cillo C, Mach J-P, Schreyer M, Carrel S. Antigenic heterogeneity of clones and subclones from human melanoma cell lines demonstrated by a panel of monoclonal antibodies and flow microfluorometry analysis. Int J Cancer. 1984;34:11. doi: 10.1002/ijc.2910340104. [DOI] [PubMed] [Google Scholar]
- 7.Dougherty GJ, Murdoch S, Hogg N. The function of human intercellular adhesion molecule-1 (ICAM-1) in the generation of an immune response. Eur J Immunol. 1988;18:35. doi: 10.1002/eji.1830180107. [DOI] [PubMed] [Google Scholar]
- 8.Feinberg AP, Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983;132:6. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
- 9.Ferrone S, Imberti L, Natali PG, Schrier PI, Ruiter D. HLA antigens on tumor cells. In: Roth JA, editor. Monoclonal antibodies in cancer: advances in diagnosis and treatment. New York: Futura Publishing Company; 1986. pp. 111–139. [Google Scholar]
- 10.Ferrone S, Temponi M, Gargiulo D, Scassellati GA, Cavaliere R, Natali PG. Selection and utilization of monoclonal antibody defined melanoma associated antigens for immunoscintigraphy in patients with melanoma. In: Srivastava S, editor. Radiolabeled monoclonal antibodies for imaging and therapy, vol 152. New York and London: Plenum Press; 1988. p. 55. [Google Scholar]
- 11.Giacomini P, Veglia F, Cordiali Fei P, Rehle T, Natali PG, Ferrone S. Level of a membrane-bound high-molecularweight melanoma-associated antigen and a cytoplasmic melanoma-associated antigen in surgically removed tissues and in sera from patients with melanoma. Cancer Res. 1984;44:1281. [PubMed] [Google Scholar]
- 12.Goldberg DA. Isolation and partial characterization of theDrosophila alcohol dehydrogenase gene. Proc Natl Acad Sci USA. 1980;77:5794. doi: 10.1073/pnas.77.10.5794. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Greenwood FC, Hunter WM, Glover JS. The preparation of131I-labelled human growth hormone of high specific radioactivity. Biochem J. 1963;89:114. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Herin M, Lemoine C, Weynants P, Vessiere F, Van Pel A, Knuth A, Devos R, Boon T. Production of stable cytolytic T-cell clones directed against autologous human melanoma. Int J Cancer. 1987;39:390. doi: 10.1002/ijc.2910390320. [DOI] [PubMed] [Google Scholar]
- 15.Houghton AN, Real FX, Davis LJ, Cordon-Cardo C, Old LJ. Phenotypic heterogeneity of melanoma. Relation to the differentiation program of melanoma cells. J Exp Med. 1987;165:812. doi: 10.1084/jem.165.3.812. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Kerbel RS, Man MS. Single-step selection of unique human melanoma variants displaying unusually aggressive metastatic behavior in nude athymic mice. Invasion Metastasis. 1984;4(suppl):31. [PubMed] [Google Scholar]
- 17.Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- 18.Lapierre LA, Fiers W, Pober JS. Three distinct classes of regulatory cytokines control endothelial cell MHC antigen expression. Interactions with immune γ interferon differentiate the effects of tumor necrosis factor and lymphotoxin from those of leukocyte α and fibroblast β interferons. J Exp Med. 1988;167:794. doi: 10.1084/jem.167.3.794. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Leeuwenberg JFM, Van Damme J, Meager T, Jeunhomme TMAA, Buurman WA. Effects of tumor necrosis factor in the interferon-γ-induced major histocompatibility complex class II antigens expression by human endothelial cells. Eur J Immunol. 1988;18:1469. doi: 10.1002/eji.1830180925. [DOI] [PubMed] [Google Scholar]
- 20.Maio M, Gulwani B, Tombesi S, Langer JA, Duigou GJ, Kerbel RS, Fisher PB, Ferrone S. Differential induction by immune interferon of the gene products of the HLA-D region on the melanoma cell line MeWo and its metastatic variant MeM 50-10. J Immunol. 1988;141:913. [PubMed] [Google Scholar]
- 21.Maio M, Gulwani B, Langer JA, Kerbel RS, Duigou GJ, Fisher PB, Ferrone S. Modulation by interferons of HLA antigen, and intercellular adhesion molecule 1 expression by cultured melanoma cells with different metastatic potential. Cancer Res. 1989;49:2980. [PubMed] [Google Scholar]
- 22.Maio M, Gulwani B, Morgano A, Ferrone S Differential modulation by tumor necrosis factor and immune interferon of HLA Class II antigens expressed by melanoma cells. Int J Cancer, in press [DOI] [PubMed]
- 23.Makgoba MW, Sanders ME, Ginther Luce GE, Gugel EA, Dustin ML, Springer TA, Shaw S. Functional evidence that intercellular adhesion molecule-1 (ICAM-1) is a ligand for LFA-1-dependent adhesion in T cell-mediated cytotoxicity. Eur J Immunol. 1988;18:637. doi: 10.1002/eji.1830180423. [DOI] [PubMed] [Google Scholar]
- 24.Maniatis T, Fritsch EF, Sambrook J. Molecular cloning. A laboratory manual. NY: Cold Spring Harbor Laboratory, Cold Spring Harbor; 1982. [Google Scholar]
- 25.Matsui M, Temponi M, Ferrone S. Characterization of a monoclonal antibody-defined human melanoma-associated antigen susceptible to induction by immune interferon. J Immunol. 1987;139:2088. [PubMed] [Google Scholar]
- 26.Natali PG, Cavaliere R, Bigotti A, Nicotra MR, Russo C, Ng A-K, Giacomini P, Ferrone S. Antigenic heterogeneity of surgically removed primary and autologous metastatic human melanoma lesions. J Immunol. 1983;130:1462. [PubMed] [Google Scholar]
- 27.Natali PG, Bigotti A, Cavaliere R, Nicotra MR, Ferrone S. Phenotyping of lesions of melanocyte origin with monoclonal antibodies to melanoma-associated antigens and to HLA antigens. J Natl Cancer Inst. 1984;73:13. [PubMed] [Google Scholar]
- 28.Pellegrino MA, Ng A-K, Russo C, Ferrone S. Heterogeneous distribution of the determinants defined by monoclonal antibodies on HLA-A and B antigens bearing molecules. Transplantation. 1982;34:18. doi: 10.1097/00007890-198207000-00004. [DOI] [PubMed] [Google Scholar]
- 29.Poste G, Doll J, Fidler IJ. Interactions among clonal subpopulations affect stability of the metastatic phenotype in polyclonal populations of B16 melanoma cells. Proc Natl Acad Sci USA. 1981;78:6226. doi: 10.1073/pnas.78.10.6226. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Quaranta V, Pellegrino MA, Ferrone S. Serologic and immunochemical characterization of the specificity of four monoclonal antibodies to distinct antigenic determinants expressed on subpopulations of human Ia-like antigens. J Immunol. 1981;126:548. [PubMed] [Google Scholar]
- 31.Rothlein R, Dustin ML, Marlin SD, Springer TA. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J Immunol. 1986;137:1270. [PubMed] [Google Scholar]
- 32.Russo C, Callegaro L, Lanza E, Ferrone S. Purification of IgG monoclonal antibody by caprylic acid precipitation. J Immunol Methods. 1983;65:269. doi: 10.1016/0022-1759(83)90324-1. [DOI] [PubMed] [Google Scholar]
- 33.Russo C, Pellegrino MA, Ferrone S. A double-determinant immunoassay with monoclonal antibodies to the HLA-A,B,C complex. Transplant Proc. 1983;15:66. [Google Scholar]
- 34.Russo C, Pellegrino MA, Ferrone S. A double-determinant immunoassay to quantitate human Ia antigens. Transplant Proc. 1983;15:57. [Google Scholar]
- 35.Sood AK, Pereira D, Weissmann SM. Isolation and partial nucleotide sequence of a cDNA clone for human histocompatibility antigen HLA-B by use of an oligodeoxyucleotide primer. Proc Natl Acad Sci USA. 1981;78:616. doi: 10.1073/pnas.78.1.616. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Spits H, Borst J, Giphart M, Coligan J, Terhorst C, De Vries JE. HLA-DC antigens can serve as recognition elements for human cytotoxic T lymphocytes. Eur J Immunol. 1984;14:299. doi: 10.1002/eji.1830140404. [DOI] [PubMed] [Google Scholar]
- 37.Thomas PS. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci USA. 1980;77:5201. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Tonnelle C, DeMars R, Long EO. DOβ: a new β chain gene in HLA-D with a distinct regulation of expression. EMBO J. 1985;4:2839. doi: 10.1002/j.1460-2075.1985.tb04012.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Watson AJ, DeMars R, Trowbridge IS, Bach FH. Detection of a novel -uman class II HLA antigen. Nature. 1983;304:358. doi: 10.1038/304358a0. [DOI] [PubMed] [Google Scholar]