Potentiation of growth suppression and modulation of the antigenic phenotype in human melanoma cells by the combination of recombinant human fibroblast and immune interferons

Gary M. Graham, Ludovico Guarini, Thomas A. Moulton, Subashree Datta, Soldano Ferrone, Patrizio Giacomini, Robert S. Kerbel, Paul B. Fisher

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 (IFNβ) and immune (IFNγ) 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 IFNβ than to IFNγ 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 IFNβ plus IFNγ 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. IFNβ and IFNγ 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 IFNβ plus IFNγ 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 IFNβ or IFNγ, alone or in combination, and organ colonization and metastatic potential in nude mice was observed in the different melanoma cell lines.

Original languageEnglish
Pages (from-to)382-390
Number of pages9
JournalCancer Immunology, Immunotherapy
Volume32
Issue number6
DOIs
Publication statusPublished - Nov 1991

Fingerprint

Antigenic Modulation
Interferon-beta
Interferon-gamma
Melanoma
Phenotype
Interferons
Growth
Nude Mice
Melanoma-Specific Antigens
Histocompatibility Antigens
Histocompatibility Antigens Class II
Cell Line
Antigens
Neoplasms
Differentiation Antigens
Melanins
Fibroblasts

Keywords

  • Antigenic phenotype
  • Differentiation
  • Growth suppression
  • Human melanoma cells
  • Recombinant interferons

ASJC Scopus subject areas

  • Oncology
  • Immunology
  • Cancer Research

Cite this

Potentiation of growth suppression and modulation of the antigenic phenotype in human melanoma cells by the combination of recombinant human fibroblast and immune interferons. / Graham, Gary M.; Guarini, Ludovico; Moulton, Thomas A.; Datta, Subashree; Ferrone, Soldano; Giacomini, Patrizio; Kerbel, Robert S.; Fisher, Paul B.

In: Cancer Immunology, Immunotherapy, Vol. 32, No. 6, 11.1991, p. 382-390.

Research output: Contribution to journalArticle

Graham, Gary M. ; Guarini, Ludovico ; Moulton, Thomas A. ; Datta, Subashree ; Ferrone, Soldano ; Giacomini, Patrizio ; Kerbel, Robert S. ; Fisher, Paul B. / Potentiation of growth suppression and modulation of the antigenic phenotype in human melanoma cells by the combination of recombinant human fibroblast and immune interferons. In: Cancer Immunology, Immunotherapy. 1991 ; Vol. 32, No. 6. pp. 382-390.
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