Differential effects of recombinant human leukocyte interferons on cell surface antigen expression.
Human leukocyte (alpha) interferon (IFN-alpha) is composed of a multigene family within which at least eight different species have been expressed in Escherichia coli, isolated, and shown to exert a wide range of biological activities on different human target cells. In this study we utilized eight species of IFN-alpha (A, B, C, D, F, I, J, and K) and investigated their respective capabilities to alter the proliferation of a human breast carcinoma cell line (MCF-7). The antigens studied were all constitutively expressed on the MCF-7 cell surface: the Mr 180,000 carcinoembryonic antigen; a high molecular weight (greater than 10(6] glycoprotein, termed tumor-associated glycoprotein 72; and a major HLA histocompatibility antigen. The level of expression of each antigen was measured by the binding of monoclonal antibodies B1.1, B72.3, and W6/32, respectively. A high degree of diversity was found among the various IFN-alpha species with respect to their ability to enhance antigen expression and inhibit MCF-7 cell growth. The two most potent species, IFN-alpha A and IFN-alpha B, were found to increase the expression of tumor antigens as well as the HLA determinant by 2-5-fold. In contrast, IFN-alpha D and IFN-alpha J were virtually inactive in altering antigen expression but did inhibit the growth of MCF-7 cells. The remaining IFN-alpha species, -alpha C, -alpha F, -alpha I, and -alpha K, exerted an intermediate range of activities for both antigen enhancement and inhibition of MCF-7 cell growth. The relative ability of each species of IFN-alpha to inhibit MCF-7 cell growth appeared to be independent of their effectiveness in augmenting antigen expression. IFN-alpha D and IFN-alpha J, the two species that failed to alter tumor antigen expression, did, however, seem to interact with the interferon receptor since they inhibited MCF-7 cell growth and competed with other IFN-alpha species for the increase in carcinoembryonic antigen, tumor-associated glycoprotein 72, or HLA expression. A comparison of the concentrations of each IFN-alpha necessary to enhance antigen expression revealed that the surface HLA determinant was approximately 10-fold more sensitive to enhancement than was the tumor antigen, carcinoembryonic antigen. The individual members of the IFN-alpha family thus differ extensively in their ability to alter the level of antigen expression on the surface of MCF-7 breast carcinoma cells.(ABSTRACT TRUNCATED AT 400 WORDS)
D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000032:analysis*; D000954:Antigens, Surface / Q000032:analysis*; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology; D002272:Carcinoembryonic Antigen / Q000032:analysis*; D002460:Cell Line; D005260:Female; D006680:HLA Antigens / Q000032:analysis*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000187:drug effects; D017471:Receptors, Interferon; D011994:Recombinant Proteins / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D002272:Carcinoembryonic Antigen; D006680:HLA Antigens; D007370:Interferon Type I; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D011994:Recombinant Proteins