TSPO 缺乏会导致线粒体功能障碍，进而导致缺氧、血管生成以及促生长的代谢向胶质母细胞瘤中的糖酵解转变。
TSPO deficiency induces mitochondrial dysfunction, leading to hypoxia, angiogenesis, and a growth-promoting metabolic shift toward glycolysis in glioblastoma.
机构信息
Department of Immunology, Research Center on Pediatric Development and Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing, China.
Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
出版信息
Neuro Oncol. 2020 Feb 20;22(2):240-252. doi: 10.1093/neuonc/noz183.
BACKGROUND
The ligands of mitochondrial translocator protein (TSPO) have been widely used as diagnostic biomarkers for glioma. However, the true biological actions of TSPO in vivo and its role in glioma tumorigenesis remain elusive.
METHODS
TSPO knockout xenograft and spontaneous mouse glioma models were employed to assess the roles of TSPO in the pathogenesis of glioma. A Seahorse Extracellular Flux Analyzer was used to evaluate mitochondrial oxidative phosphorylation and glycolysis in TSPO knockout and wild-type glioma cells.
RESULTS
TSPO deficiency promoted glioma cell proliferation in vitro in mouse GL261 cells and patient-derived stem cell-like GBM1B cells. TSPO knockout increased glioma growth and angiogenesis in intracranial xenografts and a mouse spontaneous glioma model. Loss of TSPO resulted in a greater number of fragmented mitochondria, increased glucose uptake and lactic acid conversion, decreased oxidative phosphorylation, and increased glycolysis.
CONCLUSION
TSPO serves as a key regulator of glioma growth and malignancy by controlling the metabolic balance between mitochondrial oxidative phosphorylation and glycolysis.1. TSPO deficiency promotes glioma growth and angiogenesis.2. TSPO regulates the balance between mitochondrial oxidative phosphorylation and glycolysis.
背景
线粒体转位蛋白（TSPO）的配体已被广泛用作神经胶质瘤的诊断生物标志物。然而，TSPO 在体内的真正生物学作用及其在神经胶质瘤发生中的作用仍不清楚。
方法
采用 TSPO 敲除异种移植和自发性小鼠神经胶质瘤模型来评估 TSPO 在神经胶质瘤发病机制中的作用。使用 Seahorse 细胞外通量分析仪评估 TSPO 敲除和野生型神经胶质瘤细胞中的线粒体氧化磷酸化和糖酵解。
结果
TSPO 缺失促进了体外培养的小鼠 GL261 细胞和患者来源的干细胞样 GBM1B 细胞中的神经胶质瘤细胞增殖。TSPO 敲除增加了颅内异种移植和小鼠自发性神经胶质瘤模型中的神经胶质瘤生长和血管生成。TSPO 缺失导致线粒体碎片化增加、葡萄糖摄取和乳酸转化增加、氧化磷酸化减少和糖酵解增加。
结论
TSPO 通过控制线粒体氧化磷酸化和糖酵解之间的代谢平衡，成为神经胶质瘤生长和恶性程度的关键调节因子。1. TSPO 缺失促进神经胶质瘤的生长和血管生成。2. TSPO 调节线粒体氧化磷酸化和糖酵解之间的平衡。
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