Ullmann C D, Schlom J, Greiner J W
Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
J Immunother (1991). 1992 Nov;12(4):231-41. doi: 10.1097/00002371-199211000-00003.
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.
体外经白细胞介素-6(IL-6)处理的人结肠癌细胞,其细胞表面癌胚抗原(CEA)和正常组织相容性白细胞抗原(HLA)I类分子的表达水平升高。IL-6介导的中度分化结肠癌细胞系(WiDr)表面CEA表达的增加呈时间和剂量依赖性。用100 U IL-6/ml处理WiDr细胞5天,使表达CEA的细胞百分比从29%增加到>80%,并增强了HLA I类分子的表达水平。使用SDS-PAGE/蛋白质免疫印迹分析也观察到IL-6处理导致CEA表达增加,随后的Northern印迹分析显示CEA相关mRNA转录本也相应增加。在纳摩尔基础上比较IL-6、β干扰素和γ干扰素处理后CEA表达的增加情况,发现IL-6比任何一种干扰素都更有效。在用IL-6处理的11种不同人结肠肿瘤细胞系中,有5种细胞系的CEA和/或HLA I类分子表达增加。因此,IL-6可直接作用于人结肠癌细胞,选择性增加CEA和HLA I类抗原的表达,这可能为深入了解IL-6抑制体内肿瘤生长能力所涉及的机制提供一些线索。