Differential effects of recombinant human leukocyte interferons on cell surface antigen expression.

Abstract

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)

• Authors: J W Greiner, P B Fisher, S Pestka, J Schlom
• Journal: Cancer research (Cancer Res) Vol. 46 Issue 10 Pg. 4984-90 (Oct 1986) ISSN: 0008-5472 [Print] United States
• PMID: 2944575 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antigens, Neoplasm
• Antigens, Surface
• Carcinoembryonic Antigen
• HLA Antigens
• Interferon Type I
• Receptors, Immunologic
• Receptors, Interferon
• Recombinant Proteins

Topics

• Antibodies, Monoclonal (immunology)
• Antigens, Neoplasm (analysis)
• Antigens, Surface (analysis)
• Breast Neoplasms (immunology, pathology)
• Carcinoembryonic Antigen (analysis)
• Cell Line
• Female
• HLA Antigens (analysis)
• Humans
• Interferon Type I (pharmacology)
• Receptors, Immunologic (drug effects)
• Receptors, Interferon
• Recombinant Proteins (pharmacology)
• Structure-Activity Relationship