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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-SIGN is a Type II transmembrane protein that is specifically expressed on the surface of dendritic cells (DCs) and partially expressed on the surface of lymphoid macrophages. The carbohydrate recognition region (CRD) of DC-SIGN has a specific recognition of Lewis (Le) saccharide produced by aberrant glycosylation of cell surface molecular carcinoembryonic antigen (CEA) that is normally associated with colonic cells during malignancy. Immature DC cells are located in the tumor tissue and can interact with colon cancer cells, while mature DC cells are located outside the tumor tissue, which may be due to the combination of DC cells and colon cancer cells weakened the function and differentiation of DC cells, the mechanism may be Monocytes-derived DCs interfere with TLR-mediated signaling associated with DC maturation via DC-SIGN binding to colon cancer-associated Le polysaccharides. Mature DCs, but not immature DCs, activate T cells’ adaptive immune responses to tumors. Therefore, similar to the role of pathogens in DC-SIGN escape immune surveillance, tumor cells can also inhibit the function of DC through the interaction with DC-SIGN to facilitate the growth of colon tumors. The study on biochemical changes and immune evasion mechanism of DC-SIGN combined with Le Polysaccharide on colon cancer cells can provide new theoretical basis and interventional ways for the abnormal growth of tumor and its prevention and treatment of colon cancer and other CEA .