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Modulation by Interferons of HLA Antigen, High-Molecular-Weight Melanoma-associated Antigen, and Intercellular Adhesion Molecule 1 Expression by Cultured Melanoma Cells with Different Metastatic Potential¹

Department of Microbiology and Immunology [M. M., B. G., S. F.], New York Medical College, Valhalla, New York 10595; Department of Molecular Genetics and Microbiology [J. A. L.], UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854; Division of Cancer and Cell Biology [R. S. K.], Mount Sinai Hospital Research Institute, Toronto, Ontario M5G 1x5, Canada; Departments of Pathology and Urology [G. J. D., P. B. F.], Cancer Center/Institute of Cancer Research, Columbia University, College of Physicians and Surgeons, New York, New York 10032

The effect of leukocyte (IFN-), fibroblast (IFN-ß), and immune (IFN-) interferon and/or mezerein on the expression of HLA antigens and melanoma-associated antigens by the melanoma cell line MeWo and its metastatic variant MeM 50-10 was investigated, since this information may contribute to our understanding of the molecular mechanism(s) underlying the metastatic process and of the role of cell differentiation and growth suppression in the antigenic changes induced by interferon (IFN). The three types of IFN had no effect on the expression of high-molecular-weight melanoma-associated antigen, but enhanced that of HLA Class 1 antigens and of intercellular adhesion molecule 1 on MeWo and MeM 50-10 cells. The enhancing effect of IFN- was more marked than that of IFN- and IFN-ß. Furthermore IFN- enhanced the expression of intercellular adhesion molecule 1 by MeM 50-10 cells more than by MeWo cells. IFN-ß was shown for the first time to induce HLA Class II antigens; the effect of IFN-ß, like that of IFN-, is differential on the two cell lines and on the gene products of the HLA-D region. Like IFN-, IFN-ß induced only HLA-DR antigens on MeM 50-10 cells. The results of Northern blot analysis with HLA-DRß, -DQß, and -DPß probes suggest that the differential modulation of the gene products of the HLA-D region by IFN-ß and IFN- reflects transcriptional and posttranscriptional events. The differential susceptibility to modulation by IFN-ß and IFN- of HLA Class II antigens on MeWo and MeM 50-10 cells is an intrinsic property of each cell line, since only small differences were detected in the number and/or affinity of receptors on the two cell lines.

Furthermore, the lack of marked effects of mezerein on the antigen-modulating activity of the three types of IFN, in spite of an enhancement of their differentiating activity, suggests that the changes in the antigenic profile induced by IFN do not represent a differentiation-related phenomenon.

¹ This work was supported by NIH Grants AI21384, CA35675, CA37959, CA39559, and CA41233. P. B. F. is a Chernow Research Scholar.

² To whom requests for reprints should be addressed, at Department of Microbiology and Immunology, New York Medical College, Valhalla, NY 10595.

Received 11/28/88. Revised 2/16/89. Accepted 2/28/89.