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Differential Effects of Recombinant Human Leukocyte Interferons on Cell Surface Antigen Expression

Laboratory of Tumor Immunology and Biology, NIH/National Cancer Institute, Bethesda, Maryland 20892 [J. W. G., J. S.]; Department of Microbiology, Comprehensive Cancer Center/Institute of Cancer Research, Columbia University, College of Physicians and Surgeons, New York, New York 10032 [P. B. F.]; and Roche Institute of Molecular Biology, Nutley, New Jersey 07110 [S. P.]

Human leukocyte () interferon (IFN-) 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- (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 M_r 180,000 carcinoembryonic antigen; a high molecular weight (>10⁶) 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- species with respect to their ability to enhance antigen expression and inhibit MCF-7 cell growth. The two most potent species, IFN-A and IFN-B, were found to increase the expression of tumor antigens as well as the HLA determinant by 2–5-fold. In contrast, IFN-D and IFN-J were virtually inactive in altering antigen expression but did inhibit the growth of MCF-7 cells. The remaining IFN- species, -C, -F, -I, and -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- to inhibit MCF-7 cell growth appeared to be independent of their effectiveness in augmenting antigen expression. IFN-D and IFN-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- species for the increase in carcinoembryonic antigen, tumor-associated glycoprotein 72, or HLA expression. A comparison of the concentrations of each IFN- 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- family thus differ extensively in their ability to alter the level of antigen expression on the surface of MCF-7 breast carcinoma cells. The differential response of these cells to the IFN- species, which share a high degree of sequence homology and bind to the same cell membrane receptor, suggest that these biologically related compounds may differ in the biochemical and molecular signals induced distal to binding to the surface interferon receptor.

¹ To whom requests for reprints should be addressed, at Laboratory of Tumor Immunology and Biology, NIH/NCI, Bldg. 10, Room 8B07, Bethesda, MD 20892.

Received 4/10/86. Revised 6/27/86. Accepted 7/ 1/86.

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