Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Curr Pharm Des. 2011;17(23):2386-401. doi: 10.2174/138161211797249260.
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.
胶质母细胞瘤是一种高度致命的癌症，传统疗法只能提供缓解。胶质母细胞瘤的细胞异质性表现在遗传和表观遗传的变化上，既有随机模型，也有层次模型来解释细胞表型。在层次结构的顶端是一个自我更新的、致瘤性的、癌症干细胞（CSC）。CSC 的重要性在于它们对细胞毒性治疗的抵抗力、侵袭性潜力和促进血管生成的能力。因此，针对 CSC 可能会带来治疗益处，并使肿瘤对传统治疗敏感，这就要求阐明 CSC 的调节机制。人们已经关注 CSC 中的内在细胞系统，但对外在因素的认识正在不断发展。神经胶质瘤干细胞（GSCs）在功能龛中富集，特别是在血管周围空间和缺氧区域。这些龛位提供了维持 GSCs 的指示性线索，并诱导细胞向干细胞样表型发生可塑性。因此，GSC 维持龛位可能提供新的治疗靶点，但也可能显示出额外的复杂性，可能有不同的 GSC 池受不同的分子机制控制，必须针对这些机制进行肿瘤控制。
