Expression of CD133 and CD44 in glioblastoma stem cells correlates with cell proliferation, phenotype stability and intra-tumor heterogeneity.
Expression of CD133 and CD44 in glioblastoma stem cells correlates with cell proliferation, phenotype stability and intra-tumor heterogeneity.
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DOI：
10.1371/journal.pone.0172791
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Mantamadiotis T
中科院分区：
文献类型：
--
作者：
Brown DV;Filiz G;Daniel PM;Hollande F;Dworkin S;Amiridis S;Kountouri N;Ng W;Morokoff AP;Mantamadiotis T
胶质母细胞瘤（GBM）是一种异质性的脑部肿瘤，由于复发和治疗后的耐药性，预后较差。全基因组分析揭示了不同GBM分子亚型的存在，这些亚型对积极治疗的反应不同。尽管如此，分子亚型不能预测复发或耐药，不同亚型的总生存率相似。导致肿瘤复发和抵抗治疗的关键特征之一被认为是潜在的耐药胶质瘤干细胞（GSC）亚群。CD133表达已被用作GSCs的标志物，然而最近的证据表明，CD133表达、GSCs和分子亚型之间的关系比最初提出的要复杂得多。利用患者源性胶质瘤干细胞（PDGCs）在体外和体内研究了CD133、Olig2和CD44的表达。不同的PDGCs表现出不同的CD133+和CD44+亚群的特征平衡，并且还研究了环境因素对PDGCs中CD133+和CD44+细胞肿瘤内平衡的影响，其中缺氧诱导CD44+向CD133+转移，化疗诱导CD133+向CD44+转移。这些数据表明，在初始手术和复发性GBM手术中使用分子标记物监测和调节肿瘤内异质性可能对更有效地治疗GBM很重要。
Glioblastoma (GBM) is a heterogeneous tumor of the brain with a poor prognosis due to recurrence and drug resistance following therapy. Genome-wide profiling has revealed the existence of distinct GBM molecular subtypes that respond differently to aggressive therapies. Despite this, molecular subtype does not predict recurrence or drug resistance and overall survival is similar across subtypes. One of the key features contributing to tumor recurrence and resistance to therapy is proposed to be an underlying subpopulation of resistant glioma stem cells (GSC). CD133 expression has been used as a marker of GSCs, however recent evidence suggests the relationship between CD133 expression, GSCs and molecular subtype is more complex than initially proposed. The expression of CD133, Olig2 and CD44 was investigated using patient derived glioma stem-like cells (PDGCs) in vitro and in vivo. Different PDGCs exhibited a characteristic equilibrium of distinct CD133+ and CD44+ subpopulations and the influence of environmental factors on the intra-tumor equilibrium of CD133+ and CD44+ cells in PDGCs was also investigated, with hypoxia inducing a CD44+ to CD133+ shift and chemo-radiotherapy inducing a CD133+ to CD44+ shift. These data suggest that surveillance and modulation of intra-tumor heterogeneity using molecular markers at initial surgery and surgery for recurrent GBM may be important for more effective management of GBM.