title: Effect of recombinant human fibroblast interferon and mezerein on growth, differentiation, immune interferon binding and tumor associated antigen expression in human melanoma cells.
abstract: The combination of recombinant human fibroblast interferon (INF-delta) and the antileukemic compound mezerein (MEZ) results in a synergistic suppression in the growth of human melanoma cells and a concomitant increase in melanin synthesis. In the present study we have further analyzed this synergistic interaction and have also evaluated the effect of IFN-delta and MEZ, alone and in combination, on recombinant human gamma interferon (IFN-gamma) binding and Class I HLA and melanoma associated antigen (MAA) expression in the HO-1 human melanoma cell line. Single cell clones isolated from the HO-1 cell line varied in their sensitivity to the antiproliferative effects of IFN-delta and MEZ. With all twelve clones, however, the combination of IFN-delta plus MEZ was more growth inhibitory than either agent used alone, even in HO-1 subclones displaying relative resistance to IFN-delta. By continuous growth in gradually increasing concentrations of IFN-delta, a variant population of HO-1 cells, HO-1 delta R-D, was generated which was more resistant to the antigrowth effects of IFN-delta than the original HO-1 parental cell line. In the IFN delta R-D cell line the combination of IFN-delta plus MEZ synergistically suppressed growth. Exposure of HO-1 cells to 2500 units/ml IFN-delta or 50 ng/ml MEZ for 96 hr resulted in no change or an increase in the binding of labelled IFN-gamma to surface receptors, whereas the combination of IFN-delta plus MEZ increased IFN-gamma binding 2-to-4-fold in HO-1 cells. This increase was the result of an increase in the number of receptors on treated cells coupled with a protection against a decrease in receptors observed for confluent untreated cells. Changes in IFN-gamma binding resulting from treatment with IFN-delta plus MEZ were not associated with alterations in the binding affinity of INF-gamma to its receptor. Changes were also observed in the expression of HLA Class I antigens and MAAs following treatment of HO-1 cells with IFN-delta, MEZ or IFN-delta plus MEZ. IFN-delta and MEZ increased the expression of HLA Class I antigens a 96 kd MAA defined by MoAb CL203, a 100 kd MAA defined by MoAb 376.96 and a 115 kd MAA defined by MoAb 345.134 but decreased the expression of a high molecular weight-melanoma associated antigen (HMW-MAA) defined by MoAb 325.28S.(ABSTRACT TRUNCATED AT 400 WORDS)
mesh_terms: D000951:Antigens, Neoplasm; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004224:Diterpenes; D005260:Female; D006680:HLA Antigens / Q000032:analysis*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism*; D008545:Melanoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D058950:Melanoma-Specific Antigens; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D011971:Receptors, Immunologic / Q000032:analysis; D017471:Receptors, Interferon; D011994:Recombinant Proteins / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology*
chemical_list: D000951:Antigens, Neoplasm; D004224:Diterpenes; D006680:HLA Antigens; D007370:Interferon Type I; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D013729:Terpenes; C011309:mezerein; D007371:Interferon-gamma