Interleukin-6 increases carcinoembryonic antigen and histocompatibility leukocyte antigen expression on the surface of human colorectal carcinoma cells.
Human colorectal carcinoma cells that were treated in vitro with interleukin-6 (IL-6) expressed increased levels of carcinoembryonic antigen (CEA) and normal histocompatibility leukocyte antigen (HLA) class I on their cell surface. The IL-6 mediated increase of CEA expression on the surface of a moderately differentiated colon carcinoma cell line (WiDr) was time- and dose-dependent. A 5-day treatment of the WiDr cells with 100 U IL-6/ml increased the percentage of cells that expressed CEA from 29 to > 80% and enhanced the level of HLA class I expression. The increase in CEA expression as a result of IL-6 treatment was also observed using SDS-PAGE/Western blot analyses, and subsequent Northern blot analyses revealed concomitant increases in CEA-related mRNA transcripts. A comparison of the increases in CEA expression after IL-6, interferon-beta, and interferon-gamma on a nanomolar basis revealed that IL-6 was more potent than either of the interferons. Of 11 different human colorectal tumor cell lines that were treated with IL-6, CEA and/or HLA class I expression were increased in five. Thus, IL-6 can act directly on human colon carcinoma cells and selectively increase the expression of CEA and HLA class I antigens, which may provide some insight into the mechanisms involved in the ability of IL-6 to suppress in vivo tumor growth.
Ullmann
C D
CD
Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Schlom
J
J
Greiner
J W
JW
D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011971:Receptors, Immunologic / Q000032:analysis; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000951:Antigens, Neoplasm; D002272:Carcinoembryonic Antigen; D015395:Histocompatibility Antigens Class I; D015850:Interleukin-6; D009363:Neoplasm Proteins; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D016899:Interferon-beta; D007371:Interferon-gamma