Department for Immunochemistry and Glycobiology, Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Zemun-Belgrade, Serbia.
Arch Biochem Biophys. 2010 Jul;499(1-2):69-76. doi: 10.1016/j.abb.2010.05.011. Epub 2010 May 17.
Cancer antigen 125 (CA125), also referred to as mucin 16, is expressed under both normal and pathological conditions and the complexity of its structure indicates multifunctionality, i.e. both the protein and carbohydrate parts may be involved in diverse interactions at different levels of cell and tissue organization. Its biological role is not understood, but involvement in immune response modulation and influence on cell adhesion have been speculated. This study aimed at isolation and characterization of endogenous ligands for CA125 as an initial step in gaining insight into its activity. A CA125-reactive fraction was separated from human placental extract by affinity chromatography. The isolated preparation was characterized by SDS-PAGE, immunoblotting, peptide mass fingerprinting and binding assay. The CA125-reactive fraction from placental extract was identified as carbohydrate-binding IgG. The glycan composition of inhibitors of carbohydrate-binding pointed to sialic acid as one determinant for recognition but indicated that sialylation was not alone and that glycotopes containing galactose, N-acetylgalactosamine and N-acetylglucosamine were also important. CA125-reactive IgG could be selectively enriched using fetuin as the ligand and represents a distinct IgG subfraction differing from abundant natural carbohydrate-binding antibodies. Taking advantage of the particular properties of ligands for CA125 may have biomedical potential for use as biological modifiers or delivery agents and have an impact beyond pregnancy, since many immunoregulatory molecular pathways are common to embryonic development and malignant transformation.
癌抗原 125（CA125），也称为黏蛋白 16，在正常和病理条件下均有表达，其结构的复杂性表明其具有多功能性，即蛋白质和碳水化合物部分可能参与细胞和组织水平不同的多种相互作用。其生物学作用尚不清楚，但推测其参与免疫反应调节和对细胞黏附的影响。本研究旨在通过亲和层析从人胎盘提取物中分离和鉴定 CA125 的内源性配体，作为深入了解其活性的初步步骤。从胎盘提取物中分离出与 CA125 反应的部分，通过 SDS-PAGE、免疫印迹、肽质量指纹图谱和结合试验进行鉴定。胎盘提取物中与 CA125 反应的部分被鉴定为结合碳水化合物的 IgG。抑制碳水化合物结合的抑制剂的聚糖组成表明唾液酸是识别的一个决定因素，但表明唾液酸化不是唯一的，并且含有半乳糖、N-乙酰半乳糖胺和 N-乙酰葡萄糖胺的糖基也很重要。使用胎球蛋白作为配体可以选择性地富集与 CA125 反应的 IgG，这代表了一种独特的 IgG 亚群，与丰富的天然碳水化合物结合抗体不同。利用 CA125 配体的特殊性质可能具有作为生物调节剂或递药载体的医学潜力，并可能对妊娠以外的领域产生影响，因为许多免疫调节分子途径在胚胎发育和恶性转化中是共同的。
