Analysis of receptors, cell surface antigens, and proteins in human melanoma cell lines resistant to human recombinant beta- or gamma-interferon.
We studied the mechanisms of resistance to interferon (IFN) in two human melanoma cell lines, SK-MEL-28/beta cells resistant to human recombinant beta-interferon (ReIFN-beta) and SK-MEL-28/gamma cells resistant to human recombinant gamma-interferon (ReIFN-gamma). SK-MEL-28/beta cells were resistant to both ReIFN-beta and IFN-alpha, but not ReIFN-gamma or natural gamma-interferon (IFN-gamma), and SK-MEL-28/gamma cells were resistant to both ReIFN-gamma and IFN-gamma, but not ReIFN-beta or IFN-alpha. SK-MEL-28/s cells, sensitive to both ReIFN-beta and ReIFN-gamma, had receptors for ReIFN-beta and ReIFN-gamma. Furthermore ReIFN-beta and IFN-alpha shared the common receptors as judged by competition assays, while the receptors for ReIFN-gamma were independent in SK-MEL-28/s cells. The Kd values of binding of both IFNs to SK-MEL-28/beta or SK-MEL-28/gamma cells were essentially equivalent to those to SK-MEL-28/s cells. Both labeled IFNs were internalized rapidly into all cell lines at 37 degrees C. No significant difference in internalization was found between IFN-sensitive and -resistant cells. Each cell line expressed HLA-AB and Mr 97,000 protein antigens, the expressions of which were enhanced by ReIFN-beta and ReIFN-gamma. Partial resistance to the enhancement of both antigens by both IFNs was seen in the resistant cells. Finally ReIFN-gamma, but not ReIFN-beta, induced a Mr 56,000 protein in SK-MEL-28/s cells. This effect of ReIFN-gamma was also detected in SK-MEL-28/beta cells, but not SK-MEL-28/gamma cells. These results provide some information concerning the nature of IFN-resistant cells. The receptors had no significant correlation with the resistance, while the expression of HLA-AB or Mr 97,000 protein antigens or the induction of proteins had some correlation with the resistance.
D000951:Antigens, Neoplasm; D000954:Antigens, Surface / Q000032:analysis*; D002460:Cell Line; D004351:Drug Resistance; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D007372:Interferons / Q000378:metabolism / Q000494:pharmacology*; D008545:Melanoma / Q000032:analysis* / Q000276:immunology; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000032:analysis*; D011971:Receptors, Immunologic / Q000032:analysis*; D017471:Receptors, Interferon; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012845:Sindbis Virus / Q000187:drug effects; D014357:Trypsin / Q000494:pharmacology
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D006680:HLA Antigens; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D007372:Interferons; D014357:Trypsin