DC-SIGN与结肠癌的生长  

DC-SIGN and the growth of colon cancer

作　　者：张长福[1,2] 姜艳梅[3] 姜旭东[1] 丁东兵[4] 左云飞[1] 

机构地区：[1]大连医科大学检验医学院,大连116023 [2]大连医科大学临床医学七年制,大连116023 [3]大连医科大学附属第一医院三部检验科,大连116023 [4]大连医科大学附属第二医院胃肠外科,大连116023

出　　处：《生命科学》2013年第9期886-890,共5页Chinese Bulletin of Life Sciences

基　　金：国家自然科学基金项目(31270867)

摘　　要：DC-SIGN是一种特异表达于树突状细胞(DC)表面和部分表达于淋巴窦内巨噬细胞表面的II型跨膜蛋白。DC-SIGN的碳水化合物识别区(CRD)对正常结肠细胞在恶变的过程中伴随的细胞表面分子癌胚抗原(CEA)的异常糖基化而产生的Lewis(Le)糖具有特异性识别作用。未成熟的DC细胞位于肿瘤组织内,并且能与结肠癌细胞相互作用,而成熟的DC细胞位于肿瘤组织外部,这可能由于DC细胞与结肠癌细胞结合削弱DC细胞的功能及分化,其机制可能是单核细胞来源的DC细胞通过DC-SIGN与结肠癌相关的Le多糖结合后干扰了与DC成熟相关的TLR介导的信号传递作用。成熟的DC细胞而不是未成熟的DC细胞能激活T细胞对肿瘤的获得性免疫反应。因此,与病原体作用DC-SIGN逃避免疫监视类似,肿瘤细胞也可以通过与DC-SIGN的相互作用来抑制DC的功能,从而利于结肠肿瘤的生长。通过对DC-SIGN与结肠癌细胞上的Le多糖结合后发生的生化改变及免疫逃避机制的研究,可以为结肠癌及其其他CEA表达异常的肿瘤生长及其防治提供新的理论根据和干预途径。DC-specific ICAM-3-grabbing nonintegrin （DC-SIGN）, a II-type transmembrane protein specifically expressed on DCs and segmentally on lymph node sinusoidal macrophages. The carbohydrate recognition domain （CRD） of DC-SIGN recognizes Lewis （Le） glycans, which are present on colon epithelia upon malignant transformation of normal colon epithelia. Immature dendritic cells are located intratumorally within colorectal cancer and intimately interact with tumor cells, whereas mature dendritic cells are present peripherally to the tumor, which may be due to that the interactions between DCs and colon carcinoma cells impair the function and differentiation of DCs, and the mechanism is likely to be that DC-SIGN on MoDCs, upon the binding of colon cancer-associated Le glycans, interferes with TLR-mediated signaling in DC maturation. Mature DCs but not immature DCs activate the resting T cells to initiate the acquired immune responses to tumor. Therefore, similar to pathogens that target DC-SIGN to escape immunosurveillance, tumor cells may interact with DC-SIGN to suppress dendritic cell functions, which contributes to the growth of colon cancer. Studies on the biochemical changes and the mechanism of immunological escape after the interactions between DC-SIGN and Le glycans will provide us with a new method for treating and preventing the colon cancer and other tumors that express CEA abnormally.

关 键 词：DC-SIGN 结肠癌 Lewis糖 癌胚抗原 分子机制 

分 类 号：R392[医药卫生—免疫学] R735.3[医药卫生—基础医学]