title: Potentiation of growth suppression and modulation of the antigenic phenotype in human melanoma cells by the combination of recombinant human fibroblast and immune interferons.
abstract: 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 beta) and immune (IFN gamma) 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 beta than to IFN gamma 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 beta plus IFN gamma 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 beta and IFN gamma 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 beta plus IFN gamma 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 beta or IFN gamma, alone or in combination, and organ colonization and metastatic potential in nude mice was observed in the different melanoma cell lines.
authors.affiliation: Department of Neurosurgery, Columbia University, College of Physicians and Surgeons, New York, New York 10032.
authors.forename: G M
authors.initials: GM
authors.lastname: Graham
authors.forename: L
authors.initials: L
authors.lastname: Guarini
authors.forename: T A
authors.initials: TA
authors.lastname: Moulton
authors.forename: S
authors.initials: S
authors.lastname: Datta
authors.forename: S
authors.initials: S
authors.lastname: Ferrone
authors.forename: P
authors.initials: P
authors.lastname: Giacomini
authors.forename: R S
authors.initials: RS
authors.lastname: Kerbel
authors.forename: P B
authors.initials: PB
authors.lastname: Fisher
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006680:HLA Antigens / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1; D007370:Interferon Type I / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000627:therapeutic use*; D008543:Melanins / Q000096:biosynthesis; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins / Q000627:therapeutic use; D013729:Terpenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D000972:Antineoplastic Agents, Phytogenic; D015815:Cell Adhesion Molecules; D004224:Diterpenes; D006680:HLA Antigens; D007370:Interferon Type I; D008543:Melanins; D011994:Recombinant Proteins; D013729:Terpenes; D018799:Intercellular Adhesion Molecule-1; C011309:mezerein; D007371:Interferon-gamma