《生命科学》 2013, 25(9): 886-890

DC-SIGN与结肠癌的生长

张长福^1，2，姜艳梅³，姜旭东¹，丁东兵⁴，左云飞^1*

(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)
    

摘　要：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。
    关键词：DC-SIGN ；结肠癌；Lewis 糖；癌胚抗原；分子机制

DC-SIGN and the growth of colon cancer

ZHANG Chang-Fu^1，2， JIANG Yan-Mei³， JIANG Xu-Dong¹， DING Dong-Bing⁴， ZUO Yun-Fei^1*

(1 Department of Clinical Laboratory， Dalian Medical University， Dalian 116023， China; 2 The Seven-Year Clinical Medicine， Dalian Medical University， Dalian 116023， China; 3 Three Clinical Laboratory， First Affiliated Hospital， Dalian Medical University， Dalian 116023， China;4 Department of Gastrointestinal Surgery， Second Affiliated Hospital， Dalian Medical University， Dalian 116023， China)
    

Abstract: Abstract: 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.
    Key words: DC-SIGN; colon cancer; Lewis glycans; CEA; molecular mechanism