Yi Fu1, Dongdong Wang1, Huaishan Wang1, Menghua Cai1, Chao Li1, Xue Zhang1, Hui Chen1, Yu Hu1, Xuan Zhang2, Mingyao Ying3, Wei He1, Jianmin Zhang1. 1. 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. 2. Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 3. Hugo W. Moser Research Institute at Kennedy Krieger, and Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Abstract
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.
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 mouseglioma 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 mouseGL261 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.
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