Centre for Evolution and Cancer & Division of Molecular Pathology, The Institute of Cancer Research, London SM2 5NG, UK.
Immune Regulation and Tumor Immunotherapy Group, Cancer Immunology Unit, Research Department of Haematology, UCL Cancer Institute, London WC1E 6DD, UK.
Semin Cancer Biol. 2023 Jul;92:139-149. doi: 10.1016/j.semcancer.2023.04.004. Epub 2023 Apr 8.
Quiescence is a state of cell cycle arrest, allowing cancer cells to evade anti-proliferative cancer therapies. Quiescent cancer stem cells are thought to be responsible for treatment resistance in glioblastoma, an aggressive brain cancer with poor patient outcomes. However, the regulation of quiescence in glioblastoma cells involves a myriad of intrinsic and extrinsic mechanisms that are not fully understood. In this review, we synthesise the literature on quiescence regulatory mechanisms in the context of glioblastoma and propose an ecological perspective to stemness-like phenotypes anchored to the contemporary concepts of niche theory. From this perspective, the cell cycle regulation is multiscale and multidimensional, where the niche dimensions extend to extrinsic variables in the tumour microenvironment that shape cell fate. Within this conceptual framework and powered by ecological niche modelling, the discovery of microenvironmental variables related to hypoxia and mechanosignalling that modulate proliferative plasticity and intratumor immune activity may open new avenues for therapeutic targeting of emerging biological vulnerabilities in glioblastoma.
静止是细胞周期停滞的一种状态，使癌细胞能够逃避抗增殖的癌症治疗。静止的癌症干细胞被认为是胶质母细胞瘤（一种侵袭性脑癌，患者预后不良）治疗耐药的原因。然而，胶质母细胞瘤细胞静止的调节涉及到许多内在和外在的机制，这些机制还不完全清楚。在这篇综述中，我们综合了关于胶质母细胞瘤中静止调节机制的文献，并提出了一种生态观点，将类似于干性的表型锚定在当代的小生境理论概念上。从这个角度来看，细胞周期的调节是多尺度和多维的，小生境的维度扩展到肿瘤微环境中的外在变量，这些变量决定着细胞的命运。在这个概念框架内，并借助生态小生境模型，发现与缺氧和机械信号转导相关的微环境变量可以调节增殖可塑性和肿瘤内免疫活性，这可能为靶向胶质母细胞瘤中新兴生物学脆弱性的治疗开辟新途径。
