Potentiation of growth suppression and modulation of the antigenic phenotype in human melanoma cells by the combination of recombinant human fibroblast and immune interferons |
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Authors: | Gary M Graham Ludovico Guarini Thomas A Moulton Subashree Datta Soldano Ferrone Patrizio Giacomini Robert S Kerbel Paul B Fisher |
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Institution: | (1) Departments of Neurosurgery, Pathology and Urology, Columbia University, College of Physicians and Surgeons, 650 West 168th Street, 10 032 New York, NY, USA;(2) Division of Pediatric Hematology/Oncology, Comprehensive Cancer Center/Institute of Cancer Research, Columbia University, College of Physicians and Surgeons, 10 032 New York, New York, USA;(3) Department of Microbiology and Immunology, New York Medical College, 10 595 Valhalla, New York, USA;(4) Immunology Laboratory, Regina Elena Institute, 00 161 Rome, Italy;(5) Division of Cancer and Cell Biology, Mt. Sinai Hospital Research Institute, M5G 1X5 Toronto, Ontario, Canada |
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Abstract: | Summary Administration of interferon as a single therapeutic regimen in cancer patients with various neoplasias has had only limited efficacy in ameliorating the negative clinical course of their disease. In the present study, we have evaluated the effect of recombinant human fibroblast (IFN ) and immune (IFN ) interferon, alone and in combination, on growth, differentiation and the expression of class I and II histocompatibility locus antigens (HLA) and melanoma-associated antigens on the human melanoma cell line H0-1. The effect of combinations of interferons on the antigenic profile of human melanoma cells displaying different organ colonization and spontaneous metastatic potential in athymic nude mice was also determined. H0-1 cells were more sensitive to the antiproliferative activity of IFN than to IFN and the combination of interferons resulted in a potentiation of growth suppression. The antiproliferative effect of both interferons was greater in later-passage than in earlier-passage H0-1 cells, possibly reflecting alterations in the evolving tumor cell population as a result of long-term in vitro propagation and/or the selective outgrowth of cells with an increased growth rate. The enhanced growth suppression observed in H0-1 cells treated with the combination of IFN plus IFN was not associated with a significant increase in the level of melanin, a marker of melanoma differentiation, above that observed with either interferon used alone. IFN and IFN differentially modulated the expression of class I and II HLA and melanoma-associated antigens in H0-1 cells and a series of melanoma cells with different organ colonization and metastatic potential, including MeWo, MeM 50-10, MeM 50-17, 3S5 and 70W. No consistent potentiation or antagonism in the expression of any specific antigen was observed in any of the melanoma cell lines exposed to the combination of interferons. The present study demonstrates that the combination of IFN plus IFN can potentiate growth suppression in H0-1 human melanoma cells and that this effect is not associated with an increase in differentiation or a potentiation in antigenic modulation. In addition, no direct correlation between the expression of any specific antigen or its modulation by IFN or IFN , alone or in combination, and organ colonization and metastatic potential in nude mice was observed in the different melanoma cell lines. |
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Keywords: | Human melanoma cells Recombinant interferons Growth suppression Differentiation Antigenic phenotype |
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