Glioblastoma stem cells (GSCs) epigenetic plasticity and interconversion between differentiated non-GSCs and GSCs.
Glioblastoma stem cells (GSCs) epigenetic plasticity and interconversion between differentiated non-GSCs and GSCs.
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DOI：
10.1016/j.gendis.2015.02.001
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发表时间：
2015-06
期刊：
影响因子：
6.8
通讯作者：
Bijangi-Vishehsaraei, Khadijeh
中科院分区：
文献类型：
--
作者：
Safa, Ahmad R;Saadatzadeh, Mohammad Reza;Cohen-Gadol, Aaron A;Pollok, Karen E;Bijangi-Vishehsaraei, Khadijeh
肿瘤干细胞（cancer stem cells，CSC）或肿瘤起始细胞（cancer initiating cells，CIC）维持着各种肿瘤的自我更新和多谱系分化特性，以及肿瘤内由几个亚群组成的细胞异质性。CSC显示恶性表型、自我更新能力、改变的基因组稳定性、特异性表观遗传标记，并且大多数时间可以通过细胞表面标志物（例如，CD 133、CD 24和CD 44）。许多研究支持非干细胞癌细胞（non-CSC）对癌症治疗敏感，而CSC对治疗相对耐受的概念。在胶质母细胞瘤干细胞（GSC）中，在遗传水平上存在克隆异质性，具有不同的致瘤潜力，并且由于克隆进化而导致明确的GSC标志物表达，这可能影响疾病进展和对治疗的反应。多形性胶质母细胞瘤（GBM）肿瘤的另一个复杂性水平是GSC和分化的非GSC之间的动态平衡，以及非GSC由于表观遗传改变而回复（去分化）为GSC的潜力，表观遗传改变赋予肿瘤细胞群体表型可塑性。此外，将分化的GBM细胞暴露于治疗剂量的替莫唑胺（TMZ）或电离辐射（IR）增加了体外和体内的GSC库。本文综述了GBM的各种亚型，讨论了CSC模型的演变和表观遗传可塑性，以及GSC和分化的非GSC之间的相互转换，并提供了潜在的消除GSC的策略。
Cancer stem cells (CSCs) or cancer initiating cells (CICs) maintain self-renewal and multilineage differentiation properties of various tumors, as well as the cellular heterogeneity consisting of several subpopulations within tumors. CSCs display the malignant phenotype, self-renewal ability, altered genomic stability, specific epigenetic signature, and most of the time can be phenotyped by cell surface markers (e.g., CD133, CD24, and CD44). Numerous studies support the concept that non-stem cancer cells (non-CSCs) are sensitive to cancer therapy while CSCs are relatively resistant to treatment. In glioblastoma stem cells (GSCs), there is clonal heterogeneity at the genetic level with distinct tumorigenic potential, and defined GSC marker expression resulting from clonal evolution which is likely to influence disease progression and response to treatment. Another level of complexity in glioblastoma multiforme (GBM) tumors is the dynamic equilibrium between GSCs and differentiated non-GSCs, and the potential for non-GSCs to revert (dedifferentiate) to GSCs due to epigenetic alteration which confers phenotypic plasticity to the tumor cell population. Moreover, exposure of the differentiated GBM cells to therapeutic doses of temozolomide (TMZ) or ionizing radiation (IR) increases the GSC pool both in vitro and in vivo. This review describes various subtypes of GBM, discusses the evolution of CSC models and epigenetic plasticity, as well as interconversion between GSCs and differentiated non-GSCs, and offers strategies to potentially eliminate GSCs.