Characterization of the oligosaccharides associated with the human ovarian tumor marker CA125
Characterization of the oligosaccharides associated with the human ovarian tumor marker CA125
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DOI：
10.1074/jbc.m302741200
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发表时间：
2003-08-01
影响因子：
4.8
通讯作者：
Patankar, MS
中科院分区：
文献类型：
--
作者：
Wong, NK;Easton, RL;Patankar, MS
CA125 是一种粘蛋白，通常用作上皮性卵巢癌的诊断标记物。诱导对 CA125 的体液反应可延长这种癌症患者的生存时间，表明这种粘蛋白在肿瘤进展中具有潜在作用。在这项研究中，对源自人卵巢肿瘤细胞系 OVCAR-3 的 CA125 连接的寡糖进行了严格的生物物理分析。 O-聚糖的测序表明存在 1 型核心聚糖和 2 型核心聚糖。一个不寻常的特征是核心 2 型聚糖中分支核心 1 天线的表达。 CA125 也是 N-糖基化的，主要表达高甘露糖和复杂的平分型 N-连接聚糖。高甘露糖型聚糖包括Man(5)-Man(9)GlcNAc(2)。主要的N-聚糖是二触角、三触角和四触角平分型寡糖。值得注意的是，CA125 和包膜糖蛋白 gp120（源自长期感染 HIV-1 的 H9 类淋巴母细胞）的 N-糖基化谱非常相似。 CA125 相关的 N-聚糖最近还与细胞介导的免疫反应的先天性和适应性臂中涉及的关键识别事件有关。因此，CA125可能通过利用其碳水化合物序列作为功能基团诱导特异性免疫调节作用，从而促进肿瘤进展。针对 CA125 的免疫疗法可能会减弱这些免疫抑制作用，从而延长患有这种极其严重的癌症的患者的生存期。
CA125 is a mucin commonly employed as a diagnostic marker for epithelial ovarian cancer. Induction of humoral responses to CA125 leads to increased survival times in patients with this form of cancer, suggesting a potential role for this mucin in tumor progression. In this study, oligosaccharides linked to CA125 derived from the human ovarian tumor cell line OVCAR-3 were subjected to rigorous biophysical analysis. Sequencing of the O-glycans indicates the presence of both core type 1 and type 2 glycans. An unusual feature is the expression of branched core 1 antennae in the core type 2 glycans. CA125 is also N-glycosylated, expressing primarily high mannose and complex bisecting type N-linked glycans. High mannose type glycans include Man(5)-Man(9)GlcNAc(2). The predominant N-glycans are the biantennary, triantennary, and tetraantennary bisecting type oligosaccharides. Remarkably, the N-glycosylation profiles of CA125 and the envelope glycoprotein gp120 ( derived from H9 lymphoblastoid cells chronically infected with HIV-1) are very similar. The CA125-associated N-glycans have also recently been implicated in crucial recognition events involved in both the innate and adaptive arms of the cell-mediated immune response. CA125 may therefore induce specific immunomodulatory effects by employing its carbohydrate sequences as functional groups, thereby promoting tumor progression. Immunotherapy directed against CA125 may attenuate these immunosuppressive effects, leading to the prolonged survival of patients with this extremely serious form of cancer.