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Modulation of Carcinoembryonic Antigen Messenger RNA Levels in Human Colon Carcinoma Cells by Recombinant Human -Interferon

Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892 [J. K., R. T., J. G., J. S.]; the Department of Molecular Genetics and Microbiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854 [S. P.]; the Departments of Pathology and Urology, Cancer Center/Institute of Cancer Research, Columbia University, College of Physicians and Surgeons, New York, New York 10032 [P. B. F.]; and the Divisions of Immunology and Biology, Beckman Research Institute of the City of Hope, Duarte, California 91010 [J. E. S.]

Recombinant human interferons have recently been shown to enhance tumor antigen expression, including carcinoembryonic antigen (CEA), on the surface of human carcinoma cells, which results in an increase in the targeting of antitumor monoclonal antibodies (MAb) in vivo. We report here the effect of recombinant human -interferon (HuIFN-) on the expression of human CEA and its related transcripts in several human colon carcinoma and normal human fibroblast cell lines. The colon tumor cell lines HT-29, WiDr, and LS-174T were each shown to express different constitutive levels of CEA glycopeptide, as measured by the binding of the CEA-specific MAb COL-4. Treatment with HuIFN- enhanced the level of binding of COL-4 in total cell extracts of HT-29 and WiDr cells 2.5- and 6.5-fold, respectively. Using a CEA complementary DNA probe, this increase in MAb binding was shown to be accompanied by a 6- to 11-fold increase in the steady state levels of three CEA transcripts with sizes of 4.2, 3.5, and 2.8 kilobases. On the other hand, HuIFN- treatment had no effect on the level of COL-4 binding or expression of CEA transcripts in LS-174T colon carcinoma cells, which are high constitutive expressors of CEA glycoprotein. Normal human fibroblast cell lines MRC-5 and WI38 had no detectable cytoplasmic CEA glycopeptide levels nor did they contain detectable levels of CEA mRNA, either before or after treatment with HuIFN-. In contrast, HuIFN- induced the de novo expression of the normal major histocompatibility complex class II antigen, HLA-DR, on HT-29 and WiDr colon cancer cells as well as the two fibroblast cell lines. Treatment of the LS-174T cell line with HuIFN- did not result in the induction of class II HLA-DR antigen. These observations suggest that some common factors may be involved in the regulation of the CEA and class II histocompatibility genes. In addition, the demonstration that HuIFN- enhances CEA expression in some carcinoma cell lines but fails to induce de novo expression of CEA transcripts in fibroblasts supports the potential application of HuIFN- in enhancement of tumor targeting of antitumor MAbs and adds to our understanding of the mechanism of -interferon-mediated up-regulation of some tumor antigens.

¹ Chernow Research Scholar in the Department of Pathology and Urology of Columbia University, College of Physicians and Surgeons. This work was supported in part by Grant CA 37808 from the National Cancer Institute.

² To whom requests for reprints should be addressed, at the Laboratory of Tumor Immunology and Biology, National Cancer Institute, Building 10, Room 8B-07, NIH, Bethesda, MD 20892.

Received 10/ 6/88. Revised 1/27/89. Accepted 2/13/89.

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