Glioma stem cell maintenance: the role of the microenvironment.
Glioma stem cell maintenance: the role of the microenvironment.
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DOI：
10.2174/138161211797249260
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发表时间：
2011
影响因子：
3.1
通讯作者：
Hjelmeland AB
中科院分区：
文献类型：
--
作者：
Heddleston JM;Hitomi M;Venere M;Flavahan WA;Yang K;Kim Y;Minhas S;Rich JN;Hjelmeland AB
胶质母细胞瘤是一种高度致命的癌症，传统的治疗方法只能起到缓解作用。胶质母细胞瘤的细胞异质性表现在遗传和表观遗传变异上，细胞表型由随机模型和层次模型决定。在层级结构的顶端是一种自我更新、致癌的癌症干细胞(CSC)。CSCs对细胞毒治疗的抵抗力、侵袭潜能和促进血管生成的作用突出了它们的重要性。因此，靶向CSC可能提供治疗益处，并使肿瘤对常规治疗敏感，这要求阐明CSC的调控。CSCs的内在细胞系统已经引起了人们的关注，但对外部因素的认识正在发展。胶质瘤干细胞(GSCs)主要分布在血管周围空间和缺氧区。这些小生境为维持GSCs和诱导细胞向干细胞样表型的可塑性提供了有益的线索。因此，维持GSC的小生境可能提供新的治疗靶点，但也表明了额外的复杂性，可能不同的GSC池由不同的分子机制控制，必须针对肿瘤控制。
Glioblastomas are highly lethal cancers for which conventional therapies provide only palliation. The cellular heterogeneity of glioblastomas is manifest in genetic and epigenetic variation with both stochastic and hierarchical models informing cellular phenotypes. At the apex of the hierarchy is a self-renewing, tumorigenic, cancer stem cell (CSC). The significance of CSCs is underscored by their resistance to cytotoxic therapies, invasive potential, and promotion of angiogenesis. Thus, targeting CSCs may offer therapeutic benefit and sensitize tumors to conventional treatment, demanding elucidation of CSC regulation. Attention has been paid to intrinsic cellular systems in CSCs, but recognition of extrinsic factors is evolving. Glioma stem cells (GSCs) are enriched in functional niches—prominently the perivascular space and hypoxic regions. These niches provide instructive cues to maintain GSCs and induce cellular plasticity towards a stem-like phenotype. GSC-maintaining niches may therefore offer novel therapeutic targets but also signal additional complexity with perhaps different pools of GSCs governed by different molecular mechanisms that must be targeted for tumor control.