胶质瘤干细胞在肿瘤微环境中代谢调控的研究进展
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摘要
胶质瘤干细胞(GSCs)具有自我更新、多分化的能力,并认为可能是肿瘤发生、复发、高耐药性及产生异质性的主要原因,其不仅推动肿瘤发展,而且能在恶劣环境下维持肿瘤的生存。GSCs与其所处微环境间的相互作用是其发挥"干性特征"的关键因素,两者间的相互调控能激活多种细胞信号通路增强细胞对低氧的耐受,促进血管生成、侵袭、转移,增强免疫逃避等能力。因此,深入了解GSCs与肿瘤微环境间的调控机制,可为胶质瘤治疗方案的探索提供新思路。
Glioma stem cells( GSCs) have the ability of self-renewal and differentiation,and may be the main cause of tumorigenesis,recurrence,high resistance and heterogeneity. GSCs not only promote tumor development,but also maintain tumor survival in harsh environments. The interaction between GSCs and their microenvironment is the key factor for their " stem characteristics". Through mutual regulation,they can activate a variety of cell signaling pathways to enhance cell hypoxia tolerance; promote angiogenesis,invasion,metastasis; enhance immune evasion and other abilities. Therefore,an in-depth understanding of the regulatory mechanisms between GSCs and the tumor microenvironment will help to find new ways in the treatment of glioma.
Glioma stem cells( GSCs) have the ability of self-renewal and differentiation,and may be the main cause of tumorigenesis,recurrence,high resistance and heterogeneity. GSCs not only promote tumor development,but also maintain tumor survival in harsh environments. The interaction between GSCs and their microenvironment is the key factor for their " stem characteristics". Through mutual regulation,they can activate a variety of cell signaling pathways to enhance cell hypoxia tolerance; promote angiogenesis,invasion,metastasis; enhance immune evasion and other abilities. Therefore,an in-depth understanding of the regulatory mechanisms between GSCs and the tumor microenvironment will help to find new ways in the treatment of glioma.
引文
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[13] Li Z,Bao S,Wu Q, et al. Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells[J].Cancer Cell,2009,15(6):501-513.
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[17] Kreso A, Dick JE. Evolution of the cancer stem cell model[J].Cell Stem Cell,2014,14(3):275-291.
[18] Ishii A,Kimura T,Sadahiro H,et al. Histological Characterization of the Tumorigenic"Peri-Necrotic Niche"Harboring Quiescent Stem-Like Tumor Cells in Glioblastoma[J]. PLoS One,2016,11(1):e0147366.
[19] Sharma A, Shiras A. Cancer stem cell-vascular endothelial cell interactions in glioblastoma[J]. Biochem Biophys Res Commun,2016,473(3):688-692.
[20] Grivennikov SI,Greten FR,Karin M. Immunity,inflammation,and cancer[J]. Cell,2010,140(6):883-899.
[21] Nakano I, Gamier D,Minata M,et al. Extracellular vesicles in the biology of brain tumour stem cells-Implications for inter-cellular communication,therapy and biomarker development[J]. Semin Cell Dev Biol,2015,40:17-26.
[22] Tan AS,Baty JW,Dong LF,et al. Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA[J]. Cell Metab,2015,21(1):81-94.
[23] Pasquier J, Guerrouahen BS, Al TH,et al. Preferential transfer of mitochondria from endothelial to cancer cells through tunneling nanotubes modulates chemoresistance[J]. J Transl Med,2013,11:94.
[24] Yi L,Xiao H,Xu M,et al. Glioma-initiating cells:A predominant role in microglia/macrophages tropism to glioma[J]. J Neuroimmunol,2011,232(1/2):75-82.
[25] Agnihotri S,Zadeh G. Metabolic reprogramming in glioblastoma:The influence of cancer metabolism on epigenetics and unanswered questions[J]. Neuro Oncol,2016, 18(2):160472.
[26] Mashimo T,Pichumani K,Vemireddy V,et al. Acetate is a bioenergetic substrate for human glioblastoma and brain metastases[J].Cell,2014,159(7):16034614.
[27] Wang X, Yang K,Xie Q,et al. Purine synthesis promotes maintenance of brain tumor initiating cells in glioma[J]. Nat Neurosci,2017,20(5):661-673.
[28] Vlashi E,Lagadec C,Vergnes L,et al. Metabolic state of gliomastem cells and nontumorigenic cells[J]. Proc Natl Acad Sci U S A,2011,108(38):16062-16067.
[29] Barron CC, Bilan PJ,Tsakiridis T,et al. Facilitative glucose transporters:Implications for cancer detection, prognosis and treatment[J]. Metabolism,2016, 65(2):124-439.
[30] Mueckler M,Thorens B. The SLC2(GLUT)family of membrane transporters[J]. Mol Aspects Med,2013,34(2/3):121-138.
[31] Macheda ML, Rogers S, Best JD. Molecular and cellular regulation of glucose transporter(GLUT)proteins in cancer[J]. J Cell Physiol,2005,202(3):654-662.
[32] Labak CM, Wang PY, Arora R, et al. Glucose transport:Meeting the metabolic demands of cancer, and applications in glioblastoma treatment[J]. Am J Cancer Res,2016,6(8):1599-1608.
[33] Han D, Wei W, Chen X, et al. NF-κB/RelA-PKM2 mediates inhibition of glycolysis by fenofibrate in glioblastoma cells[J].Oncotarget,2015,6(28):26119-26128.
[34] Flavahan WA,Wu Q,Hitomi M,et al. Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake[J].Nat Neurosci,2013,16(10):13734382.
[35] Yuen CA,Asuthkar S,Guda MR,et al. Cancer stem cell molecular reprogramming of the Warburg effect in glioblastomas:A new target gleaned from an old concept[J].CNS Oncol,2016,5(2):101-408.
[36] Wang G,Wang J,Zhao H,et al. The role of Myc and let-7a in glioblastoma,glucose metabolism and response to therapy[J].Arch Biochem Biophys,2015,580:84-92.
[37] Katsetos CD,Anni H, Draber P. Mitochondrial dysfunction in gliomas[J]. Semin Pediatr Neurol,2013,20(3):216-227.
[38] Xie Q, Wu Q, Horbinski CM, et al. Mitochondrial control by DRP1 in brain tumor initiating cells[J]. Nat Neurosci,2015,18(4):501-510.
[39] De Luca A, Fiorillo M, Peiris-Pages M, et al. Mitochondrial biogenesis is required for the anchorage-independent survival and propagation of stem-like cancer cells[J].Oncotarget,2015,6(17):14777-14795.
[40] Cirillo A,Di SA,Petillo O,et al. High grade glioblastoma is associated with aberrant expression of ZFP57,a protein involved in gene imprinting, and of CPT1A and CPT1C that regulate fatty acid metabolism[J]. Cancer Biol Ther,2014,15(6):735-741.
[41] Lin H,Patel S, Affleck VS,et al. Fatty acid oxidation is required for the respiration and proliferation of malignant glioma cells[J].Neuro Oncol,2017,19(1):43-54.
[42] Sun P,Xia S, Lal B,et al. Lipid metabolism enzyme ACSVL3 supports glioblastoma stem cell maintenance and tumorigenicity[J].BMC Cancer,2014,14:401.
[43] Pei Z,Sun P, Huang P,et al. Acyl-CoA synthetase VL3 knockdown inhibits human glioma cell proliferation and tumorigenicity[J].Cancer Res,2009,69(24):9175-9182.
[44] Villa GR,Hulce JJ,Zanca C,et al. An LXR-Cholesterol AxisCreates a Metabolic Co-Dependency for Brain Cancers[J].Cancer Cell,2016,30(5):683-693.
[45] Kucharzewska P, Christianson HC, Belting M. Global profiling of metabolic adaptation to hypoxic stress in human glioblastoma cells[J].PLoS One,2015,10(1):e0116740.
[46] Ogunrinu TA,Sontheimer H. Hypoxia increases the dependence of glioma cells on glutathione[J]. J Biol Chem, 2010,285(48):37716-37724.
[47] Karpel-Massler G, Ramani D,Shu C,et al. Metabolic reprogramming of glioblastoma cells by L-asparaginase sensitizes for apoptosis in vitro and in vivo[J]. Oncotarget,2016,7(23):33512-33528.
[48] Rosi A, Ricci-Vitiani L, Biffoni M, et al.~1H NMR spectroscopy of glioblastoma stem-like cells identifies alpha-aminoadipate as a marker of tumor aggressiveness[J]. NMR Biomed,2015,28(3):317-326.
[49] Prinz M, Priller J. The role of peripheral immune cells in the CNS in steady state and disease[J]. Nat Neurosci, 2017, 20(2):136-144.
[50] Mantovani A,Sozzani S,Locati M,et al. Macrophage polarization:Tumor-associated macrophages as a paradigm for polarized M2mononuclear phagocytes[J]. Trends Immunol,2002, 23(11):549-555.
[51] Paulus W, Baur I, Huettner C,et al. Effects of transforming growth factor-beta 1 on collagen synthesis, integrin expression,adhesion and invasion of glioma cells[J]. J Neuropathol Exp Neurol,1995,54(2):236-244.
[52] Zhang J, Sarkar S, Cua R, et al. A dialog between glioma and microglia that promotes tumor invasiveness through the CCL2/CCR2/interleukin-6 axis[J]. Carcinogenesis,2012,33(2):312-319.
[53] Brandenburg S, Muller A,Turkowski K,et al. Resident microglia rather than peripheral macrophages promote vascularization in brain tumors and are source of alternative pro-angiogenic factors[J]. Acta Neuropathol,2016,131(3):365-378.
[54] Kuratsu J, Yoshizato K, Yoshimura T,et al. Quantitative study of monocyte chemoattractant protein-1(MCP-1)in cerebrospinal fluid and cyst fluid from patients with malignant glioma[J].J Natl Cancer Inst, 1993,85(22):1836-1839.
[55] Sun W,Li WJ,Wei FQ, et al. Blockade of MCP-1/CCR4 signaling-induced recruitment of activated regulatory cells evokes an antitumor immune response in head and neck squamous cell carcinoma[J]. Oncotarget,2016,7(25):37714-37727.
[56] Wang T,Liu G,Wang R. The Intercellular Metabolic Interplay between Tumor and Immune Cells[J]. Front Immunol,2014,5:358.
[57] Frei K, Lins H, Schwerdel C,et al. Antigen presentation in the central nervous system. The inhibitory effect of IL-40 on MHC classⅡexpression and production of cytokines depends on the inducing signals and the type of cell analyzed[J]. J Immunol,1994,152(6):2720-2728.
[58] Zhang L,Alizadeh D,Van Handel M,et al. Stat3 inhibition activates tumor macrophages and abrogates glioma growth in mice[J]. Glia,2009,57(13):1458-4467.
[59] Sato T,Terai M, Tamura Y,et al. Interleukin 10 in the tumor microenvironment:A target for anticancer immunotherapy[J].Immunol Res,2011,51(2/3):170-182.
[60] Kostianovsky AM,Maier LM, Anderson RC,et al. Astrocytic regulation of human monocytic/microglial activation[J]. J Immunol,2008,181(8):5425-5432.
[61] Thomas TM, Yu JS. Metabolic regulation of glioma stem-like cells in the tumor micro-environment[J]. Cancer Lett,2017,408:174-181.
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