Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Non-integrin (DC-SIGN) Recognizes a Novel Ligand, Mac-2-binding Protein, Characteristically Expressed on Human Colorectal Carcinomas
Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Non-integrin (DC-SIGN) Recognizes a Novel Ligand, Mac-2-binding Protein, Characteristically Expressed on Human Colorectal Carcinomas
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DOI：
10.1074/jbc.m110.215301
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发表时间：
2011-06-24
影响因子：
4.8
通讯作者：
Kawasaki, Toshisuke
中科院分区：
文献类型：
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作者：
Nonaka, Motohiro;Ma, Bruce Yong;Kawasaki, Toshisuke
树突状细胞（DC）特异性细胞间黏附分子3结合非整合素（DC - SIGN）是一种II型跨膜C型凝集素，在髓样树突状细胞和单核细胞衍生的树突状细胞（MoDCs）等树突状细胞上表达。最近，我们报道了DC - SIGN与结直肠癌细胞上表达的癌胚抗原（CEA）相互作用。CEA是结直肠癌等胃肠道癌症应用最为广泛的肿瘤标志物之一。另一方面，其他研究小组报道，在胰腺癌、乳腺癌和肺癌患者，以及人类免疫缺陷病毒和丙型肝炎病毒等病毒感染患者和自身免疫性疾病患者中，Mac - 2结合蛋白（Mac - 2BP）水平升高。在此，我们首先通过亲和层析和质谱法，鉴定出在几种结直肠癌细胞系上表达的Mac - 2BP是一种新型DC - SIGN配体。有趣的是，我们发现DC - SIGN选择性识别源自某些结直肠癌的Mac - 2BP，而不识别源自其他结直肠癌的Mac - 2BP。此外，我们发现，在与DC - SIGN结合的Mac - 2BP上表达的Le聚糖的α1 - 3,4 - 岩藻糖部分对于识别至关重要。未成熟MoDCs与结直肠癌细胞之间依赖DC - SIGN的细胞相互作用显著抑制了MoDC的功能成熟，这表明Mac - 2BP可能通过依赖DC - SIGN的识别为结直肠癌细胞提供一个致耐受的微环境。重要的是，Mac - 2BP被检测为一种主要的DC - SIGN （此处英文似乎不完整，翻译可能存在偏差）
Dendritic cell (DC)-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is a type II transmembrane C-type lectin expressed on DCs such as myeloid DCs and monocyte-derived DCs (MoDCs). Recently, we have reported that DC-SIGN interacts with carcinoembryonic antigen (CEA) expressed on colorectal carcinoma cells. CEA is one of the most widely used tumor markers for gastrointestinal cancers such as colorectal cancer. On the other hand, other groups have reported that the level of Mac-2-binding protein (Mac-2BP) increases in patients with pancreatic, breast, and lung cancers, virus infections such as human immunodeficiency virus and hepatitis C virus, and autoimmune diseases. Here, we first identified Mac-2BP expressed on several colorectal carcinoma cell lines as a novel DC-SIGN ligand through affinity chromatography and mass spectrometry. Interestingly, we found that DC-SIGN selectively recognizes Mac-2BP derived from some colorectal carcinomas but not from the other ones. Furthermore, we found that the alpha 1-3,4-fucose moieties of Le glycans expressed on DC-SIGN-binding Mac-2BP were important for recognition. DC-SIGN-dependent cellular interactions between immature MoDCs and colorectal carcinoma cells significantly inhibited MoDC functional maturation, suggesting that Mac-2BP may provide a tolerogenic microenvironment for colorectal carcinoma cells through DC-SIGN-dependent recognition. Importantly, Mac-2BP was detected as a predominant DC-SIGN