Molecular Neurotherapeutics Laboratory, National Neuroscience Institute, Singapore.
Department of Physiology, National University of Singapore, Singapore.
Biomed Res Int. 2017;2017:9634172. doi: 10.1155/2017/9634172. Epub 2017 May 28.
Glioblastoma is the most aggressive cancer of the brain. The dismal prognosis is largely attributed to the heterogeneous nature of the tumor, which in addition to intrinsic molecular and genetic changes is also influenced by the microenvironmental niche in which the glioma cells reside. The cancer stem cells (CSCs) hypothesis suggests that all cancers arise from CSCs that possess the ability to self-renew and initiate tumor formation. CSCs reside in specialized niches where interaction with the microenvironment regulates their stem cell behavior. The reciprocal interaction between glioma stem cells (GSCs) and cells from the microenvironment, such as endothelial cells, immune cells, and other parenchymal cells, may also promote angiogenesis, invasion, proliferation, and stemness of the GSCs and be likely to have an underappreciated role in their responsiveness to therapy. This crosstalk may also promote molecular transition of GSCs. Hence the inherent plasticity of GSCs can be seen as an adaptive response, changing according to the signaling cue from the niche. Given the association of GSCs with tumor recurrence and treatment sensitivity, understanding this bidirectional crosstalk between GSCs and its niche may provide a framework to identify more effective therapeutic targets and improve treatment outcome.
胶质母细胞瘤是最具侵袭性的脑癌。这种预后不良的情况在很大程度上归因于肿瘤的异质性，除了内在的分子和遗传变化外，它还受到胶质瘤细胞所在的微环境小生境的影响。癌症干细胞 (CSC) 假说表明，所有癌症都源于具有自我更新和引发肿瘤形成能力的 CSC。CSC 存在于专门的小生境中，与微环境的相互作用调节其干细胞行为。胶质瘤干细胞 (GSC) 与内皮细胞、免疫细胞和其他实质细胞等微环境细胞之间的相互作用，也可能促进血管生成、侵袭、增殖和 GSC 的干性，并可能在它们对治疗的反应中发挥未被充分认识的作用。这种串扰也可能促进 GSC 的分子转变。因此，可以将 GSC 的固有可塑性视为一种适应性反应，根据小生境的信号提示进行改变。鉴于 GSC 与肿瘤复发和治疗敏感性的关联，了解 GSC 与其小生境之间的这种双向串扰可能为确定更有效的治疗靶点和改善治疗结果提供框架。
