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黏蛋白糖链:癌症治疗的新靶点

Mucin Glycans: A Target for Cancer Therapy.

机构信息

Medical College of Yan'an University, Yan'an University, Yan'an 716000, China.

Key Laboratory of Analytical Technology and Detection of Yan'an, College of Chemistry and Chemical Engineering, Yan'an University, Yan'an 716000, China.

出版信息

Molecules. 2023 Oct 11;28(20):7033. doi: 10.3390/molecules28207033.

Abstract

Mucin glycans are an important component of the mucus barrier and a vital defence against physical and chemical damage as well as pathogens. There are 20 mucins in the human body, which can be classified into secreted mucins and transmembrane mucins according to their distributions. The major difference between them is that secreted mucins do not have transmembrane structural domains, and the expression of each mucin is organ and cell-specific. Under physiological conditions, mucin glycans are involved in the composition of the mucus barrier and thus protect the body from infection and injury. However, abnormal expression of mucin glycans can lead to the occurrence of diseases, especially cancer, through various mechanisms. Therefore, targeting mucin glycans for the diagnosis and treatment of cancer has always been a promising research direction. Here, we first summarize the main types of glycosylation (O-GalNAc glycosylation and N-glycosylation) on mucins and the mechanisms by which abnormal mucin glycans occur. Next, how abnormal mucin glycans contribute to cancer development is described. Finally, we summarize MUC1-based antibodies, vaccines, radio-pharmaceuticals, and CAR-T therapies using the best characterized MUC1 as an example. In this section, we specifically elaborate on the recent new cancer therapy CAR-M, which may bring new hope to cancer patients.

摘要

黏蛋白糖链是黏液屏障的重要组成部分,对于抵抗物理和化学损伤以及病原体具有重要的防御作用。人体内有 20 种黏蛋白,根据其分布可分为分泌型黏蛋白和跨膜型黏蛋白。它们的主要区别在于分泌型黏蛋白没有跨膜结构域,而且每种黏蛋白的表达都是器官和细胞特异性的。在生理条件下,黏蛋白糖链参与黏液屏障的组成,从而保护身体免受感染和损伤。然而,黏蛋白糖链的异常表达可通过多种机制导致疾病的发生,尤其是癌症。因此,针对黏蛋白糖链进行癌症的诊断和治疗一直是一个很有前途的研究方向。在这里,我们首先总结了黏蛋白上主要的糖基化类型(O-GalNAc 糖基化和 N-糖基化)以及异常黏蛋白糖链发生的机制。接下来,我们描述了异常黏蛋白糖链如何促进癌症的发展。最后,我们以研究最充分的 MUC1 为例,总结了基于 MUC1 的抗体、疫苗、放射性药物和 CAR-T 疗法。在这一部分,我们特别详细阐述了最近新的癌症治疗 CAR-M,它可能为癌症患者带来新的希望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/436b/10609567/9a6d32a90038/molecules-28-07033-g003.jpg

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