Dynamic alterations in serum IgG N-glycan profiles in the development of colitis-associated colon Cancer in mouse model

Dynamic alterations in serum IgG N-glycan profiles in the development of colitis-associated colon Cancer in mouse model
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小鼠模型结肠炎相关结肠癌发生过程中血清 IgG N-聚糖谱的动态变化

DOI:
10.1016/j.bbagen.2020.129668
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发表时间:
2020-10-01
影响因子:
3
通讯作者:
Gu, Jianxin
Gu, Jianxin
中科院分区:
生物学3区
文献类型:
--
作者:
Gu, Yong;Han, Jing;Gu, Jianxin

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背景:血清免疫球蛋白的选择性糖基化与结直肠癌密切相关。目前,既能最大限度地减少遗传背景、环境等干扰因素在肿瘤发生发展过程中的影响,又能重点研究免疫球蛋白糖链致癌特性的动态研究尚不多见。方法:以偶氮甲烷-葡聚糖硫酸钠诱导的典型结肠炎相关结肠炎小鼠模型为模型,采用超高效液相色谱法测定结肠炎发生发展四个阶段血清免疫球蛋白N-糖链的含量。结果:在肿瘤生长过程中,7种免疫球蛋白多糖的相对丰度发生了变化,分别为单触型、核型岩藻糖、唾液酸、半乳糖和二分型。在致癌的第一阶段,一些多糖的丰度发生了变化。相应地,肿瘤组脾B淋巴细胞和不同组织中糖基转移酶的表达也低于对照组。结论:本研究是对结肠炎相关性结直肠癌动态过程中免疫球蛋白G糖基化的综合分析。据我们所知,这是首次报道小鼠脾B淋巴细胞糖基转移酶的表达与免疫球蛋白N-糖链的变化一致或不一致,并且这种变化趋势是组织非特异性的。一般意义:为鉴定与结直肠癌发生相关的免疫球蛋白糖链提供了一种新的方法,为利用小鼠研究糖链的结构和功能奠定了基础。
Background: Alternative glycosylation of serum IgG has been shown to be closely associated with colorectal cancer (CRC). Currently, a dynamic study which can not only minimize the influence of genetic background, environment and other interfering factors during cancer development, but also focus on investigating carcinogenic characteristics of IgG glycan is lacking.Methods: Serum IgG N-glycans were characterized at four stages of CRC development by ultra-performance liquid chromatography in a typical colitis-related CRC mouse model induced by azoxymethane-dextran sodium sulfate. Furthermore, the expression of related glycosyltransferases in splenic B lymphocytes at the corresponding time was also assessed.Results: The relative abundance of seven IgG glycans, which can be classified as monoantennary, core fucose, sialic acid, galactose and bisecting, was changed during tumor growth. The abundance of some glycans was altered during the first stage of cancer induction. Correspondingly, the expression of glycosyltransferases in splenic B lymphocytes and different tissues in cancer groups was also decreased compared to that in controls.Conclusions: This study represents the comprehensive analysis of IgG glycosylation in the dynamic process of colitis-associated CRC. To our knowledge, this is the first report that the expression of glycosyltransferases in mouse splenic B lymphocytes is consistent or inconsistent with the alterations of IgG N-glycans, and the variation tendency is tissue nonspecific.General Significance: Providing a novel approach to identify the IgG glycans related to the development of CRC and laying a foundation for research on structure and function of glycans using mouse.