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癌症干细胞标志物糖基化:性质、功能与意义。

Cancer stem cell marker glycosylation: Nature, function and significance.

机构信息

Institute for Glycomics, Gold Coast Campus, Griffith University, Gold Coast, QLD, 4222, Australia.

出版信息

Glycoconj J. 2017 Aug;34(4):441-452. doi: 10.1007/s10719-017-9780-9. Epub 2017 Jun 17.

DOI:10.1007/s10719-017-9780-9
PMID:28624993
Abstract

Glycans are essential for the maintenance of normal biological function, with alterations in glycan expression being a hallmark of cancer. Cancer stem cells (CSCs) are a subset of cells within a tumour capable of self-renewal, cellular differentiation and resistances to conventional therapies. As is the case with stem cells, marker proteins present on the cell surface are frequently used to identify and enrich CSCs, with the expression of these markers statistical correlating with the likelihood of cancer recurrence and overall patient survival. As such CSC markers are of high clinical relevance. The majority of markers currently used to identify CSC populations are glycoproteins, and although the diverse biological roles for many of these markers are known, the nature and function of the glycan moiety on these glycoproteins remains to be fully elucidated. This mini-review summarises our current knowledge regarding the types and extent of CSC marker glycosylation, and the various roles that these glycans play in CSC biology, including in mediating cell adhesion, metastasis, evading apoptosis, tear shear resistance, tumour growth, maintaining pluripotency, self-renewal, trafficking, maintaining stability, maintaining enzymatic activity and aiding epithelial mesenchymal transitioning. Given that CSCs markers have multiple diverse biological functions, and are potentially of significant diagnostic and therapeutic benefit the search for new markers that are uniquely expressed on CSCs is vital to selectively target/identify this subset of cancer cells. As such we have also outlined how high-throughput lectin microarrays can be used to successfully profile the glycosylation status of CSC and to identify glyco-markers unique to CSCs.

摘要

糖基化对于维持正常的生物功能至关重要,糖基化表达的改变是癌症的一个标志。癌症干细胞(CSC)是肿瘤内能够自我更新、细胞分化和抵抗常规治疗的细胞亚群。与干细胞一样,细胞表面存在的标记蛋白通常用于识别和富集 CSC,这些标记的表达与癌症复发的可能性和患者的总体存活率呈统计学相关。因此,CSC 标记物具有很高的临床相关性。目前用于识别 CSC 群体的大多数标记物都是糖蛋白,尽管许多这些标记物的生物多样性作用已经为人所知,但这些糖蛋白上糖基部分的性质和功能仍有待充分阐明。这篇迷你综述总结了我们目前对 CSC 标记物糖基化的类型和程度的了解,以及这些糖基在 CSC 生物学中的各种作用,包括介导细胞黏附、转移、逃避细胞凋亡、撕裂剪切阻力、肿瘤生长、维持多能性、自我更新、运输、维持稳定性、维持酶活性和促进上皮间质转化。鉴于 CSC 标记物具有多种不同的生物学功能,并且具有潜在的重要诊断和治疗益处,因此寻找新的独特表达于 CSCs 的标记物对于选择性靶向/识别这种癌细胞亚群至关重要。因此,我们还概述了如何使用高通量凝集素微阵列成功分析 CSC 的糖基化状态,并鉴定 CSC 特有的糖基标记物。

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