Metabolism of stromal and immune cells in health and disease

Nature

Volumn 511, Issue 7508, 2014, Pages 167-176

  Ghesquière, Bart ^a,b   Wong, Brian W ^a,b   Kuchnio, Anna ^a,b   Carmeliet, Peter ^a,b  

^a UNIVERSITY OF LEUVEN   (Belgium)

^b DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

FATTY ACID; GLUCOSE; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; VASCULOTROPIN;

CANCER; CELL ORGANELLE; DISEASE PREVALENCE; IMMUNE RESPONSE; METABOLISM;

ADAPTATION; AEROBIC METABOLISM; ANGIOGENESIS; CANCER CELL; CELL CYCLE PHASE; CELL DIFFERENTIATION; CELL FUNCTION; CELL METABOLISM; CELL PROLIFERATION; CITRIC ACID CYCLE; DIABETES MELLITUS; DISEASES; ENDOTHELIUM CELL; ENERGY YIELD; FATTY ACID SYNTHESIS; FIBROBLAST; GLUCOSE METABOLISM; GLUCOSE OXIDATION; GLYCOLYSIS; HEALTH; HUMAN; IMMUNOCOMPETENT CELL; MACROMOLECULE; MACROPHAGE; MITOCHONDRIAL VOLUME; NEOVASCULARIZATION (PATHOLOGY); NONHUMAN; OXIDATIVE PHOSPHORYLATION; OXYGEN CONSUMPTION; POLYAMINE SYNTHESIS; PRIORITY JOURNAL; REVIEW; STROMA CELL; T LYMPHOCYTE; VASCULAR ENDOTHELIUM;

ANIMALS; CELL DIFFERENTIATION; ENDOTHELIAL CELLS; GLYCOLYSIS; HUMANS; MACROPHAGES; NEOPLASMS; STROMAL CELLS; T-LYMPHOCYTES;

EID: 84904173553     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature13312     Document Type: Review

References (106)

1. Carmeliet, P. & Jain, R. K. Molecular mechanisms and clinical applications of angiogenesis. Nature 473, 298-307 (2011).
2. Rask-Madsen, C. & King, G. L. Vascular complications of diabetes: mechanisms of injury and protective factors. Cell Metab. 17, 20-33 (2013).
3. Junttila, M. R. & de Sauvage, F. J. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature 501, 346-354 (2013).
4. Galluzzi, L., Kepp, O., Vander Heiden, M. G. & Kroemer, G. Metabolic targets for cancer therapy. Nature Rev. Drug Discov. 12, 829-846 (2013).
5. Schulze, A. & Harris, A. L. How cancer metabolism is tuned for proliferation and vulnerable to disruption. Nature 491, 364-373 (2012).
6. Lunt, S. Y. & Vander Heiden, M. G. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu. Rev. Cell Dev. Biol. 27, 441-464 (2011).
7. DeBerardinis, R. J. & Thompson, C. B. Cellular metabolismand disease: what do metabolic outliers teach us? Cell 148, 1132-1144 (2012).
8. Casazza, A. et al. Tumor stroma: a complexity dictated by the hypoxic tumor microenvironment. Oncogene 33, 1743-1754 (2014).
9. Potente, M., Gerhardt, H. & Carmeliet, P. Basic and therapeutic aspects of angiogenesis. Cell 146, 873-887 (2011).
10. De Bock, K. et al. Role of PFKFB3-driven glycolysis in vessel sprouting. Cell 154, 651-663 (2013).
11. Barth, E., Stammler, G., Speiser, B. & Schaper, J. Ultrastructural quantitation of mitochondria and myofilaments in cardiac muscle from 10 different animal species including man. J. Mol. Cell. Cardiol. 24, 669-681 (1992).
12. Quintero, M., Colombo, S. L., Godfrey, A. & Moncada, S. Mitochondria as signaling organelles in the vascular endothelium. Proc. Natl Acad. Sci. USA 103, 5379-5384 (2006).
13. Chung, S. J. et al. Pyruvate protection against endothelial cytotoxicity induced by blockade of glucose uptake. J. Biochem. Mol. Biol. 37, 239-245 (2004).
14. Schoors, S. et al. Partial and transient reduction of glycolysis by PFKFB3 blockade reduces pathological angiogenesis. Cell Metab. 19, 37-48 (2014).
15. Locasale, J. W. et al. Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nature Genet. 43, 869-874 (2011).
16. Gatenby, R. A. & Gillies, R. J. Why do cancers have high aerobic glycolysis? Nature Rev. Cancer 4, 891-899 (2004).
17. Mertens, S., Noll, T., Spahr, R., Krutzfeldt, A. & Piper, H. M. Energetic response of coronary endothelial cells to hypoxia. Am. J. Physiol. 258, H689-H694 (1990).
18. Leopold, J. A. et al. Aldosterone impairs vascular reactivity by decreasing glucose- 6-phosphate dehydrogenase activity. Nature Med. 13, 189-197 (2007).
19. Leopold, J. A., Zhang, Y. Y., Scribner, A. W., Stanton, R. C. & Loscalzo, J. Glucose-6- phosphate dehydrogenase overexpression decreases endothelial cell oxidant stress and increases bioavailable nitric oxide. Arterioscler. Thromb. Vasc. Biol. 23, 411-417 (2003).
20. Spolarics, Z., Lang, C. H., Bagby, G. J. & Spitzer, J. J. Glutamine and fatty acid oxidation are the main sources of energy for Kupffer and endothelial cells. Am. J. Physiol. 261, G185-G190 (1991).
21. Polet, F. & Feron, O. Endothelial cell metabolism and tumour angiogenesis: glucose and glutamine as essential fuels and lactate as the driving force. J. Intern. Med. 273, 156-165 (2013).
22. Unterluggauer, H. et al. Premature senescence of human endothelial cells induced by inhibition of glutaminase. Biogerontology 9, 247-259 (2008).
23. Wu, G., Haynes, T. E., Li, H. & Meininger, C. J. Glutamine metabolismin endothelial cells: ornithine synthesis from glutamine via pyrroline-5-carboxylate synthase. Comp. Biochem. Physiol. Physiol. 126, 115-123 (2000).
24. Carracedo, A., Cantley, L. C. & Pandolfi, P. P. Cancer metabolism: fatty acid oxidation in the limelight. Nature Rev. Cancer 13, 227-232 (2013).
25. Dagher, Z., Ruderman, N., Tornheim, K. & Ido, Y. Acute regulation of fatty acid oxidation andAMP-activated protein kinase in humanumbilical vein endothelial cells. Circ. Res. 88, 1276-1282 (2001).
26. Schug, Z. T., Frezza, C., Galbraith, L. C. & Gottlieb, E. Themusic of lipids: how lipid composition orchestrates cellular behaviour. Acta Oncol. 51, 301-310 (2012).
27. Fang, L. et al. Control of angiogenesis by AIBP-mediated cholesterol efflux. Nature 498, 118-122 (2013).
28. Avraham-Davidi, I. et al. ApoB-containing lipoproteins regulate angiogenesis by modulating expression of VEGF receptor 1. Nature Med. 18, 967-973 (2012).
29. Seguin, F. et al. The fatty acid synthase inhibitor orlistat reduces experimental metastases and angiogenesis in B16-F10 melanomas. Br. J. Cancer 107, 977-987 (2012).
30. Merchan, J. R. et al. Antiangiogenic activity of 2-deoxy-D-glucose. PLoS ONE 5, e13699 (2010).
31. Koziel, A., Woyda-Ploszczyca, A., Kicinska, A. & Jarmuszkiewicz, W. The influence of highglucose onthe aerobicmetabolismof endothelial EA. hy926cells. Pflugers Arch. 464, 657-669 (2012).
32. Brandes, R. P., Weissmann, N. & Schroder, K. Redox-mediated signal transduction by cardiovascular Nox NADPH oxidases. J. Mol. Cell. Cardiol. 73, 70-79 (2014).
33. Du, X. et al. Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells. J. Clin. Invest. 112, 1049-1057 (2003).
34. Tang, W. H. ,Martin, K. A. & Hwa, J. Aldose reductase, oxidative stress, and diabetic mellitus. Front Pharmacol 3, 87 (2012).
35. Manigrasso, M. B., Juranek, J., Ramasamy, R. & Schmidt, A. M. Unlocking the biology of RAGE in diabetic microvascular complications. Trends Endocrinol. Metab. 25, 15-22 (2014).
36. Liu, J. et al. Aldolase B knockdown prevents high glucose-induced methylglyoxal overproduction and cellular dysfunction in endothelial cells. PLoS ONE 7, e41495 (2012).
37. Sena, C. M. et al. Methylglyoxal promotes oxidative stress and endothelial dysfunction. Pharmacol. Res. 65, 497-506 (2012).
38. Forstermann, U. & Sessa, W. C. Nitric oxide synthases: regulation and function. Eur. Heart J. 33, 829-837 (2012).
39. Beleznai, T. & Bagi, Z. Activation of hexosamine pathway impairs nitric oxide (NO)-dependent arteriolar dilations by increased protein O-GlcNAcylation. Vascul. Pharmacol. 56, 115-121 (2012).
40. Warren, C. M., Ziyad, S., Briot, A., Der, A. & Iruela-Arispe, M. L. A ligandindependent VEGFR2 signaling pathway limits angiogenic responses in diabetes. Sci. Signal. 7, ra1 (2014).
41. Hill, M. F. Emerging role for antioxidant therapy in protection against diabetic cardiac complications: experimental and clinical evidence for utilization of classic and new antioxidants. Curr. Cardiol. Rev. 4, 259-268 (2008).
42. Shah, G. N. et al. Pharmacological inhibition of mitochondrial carbonic anhydrases protects mouse cerebral pericytes from high glucose-induced oxidative stress and apoptosis. J. Pharmacol. Exp. Ther. 344, 637-645 (2013).
43. Luo, B., Soesanto, Y. & McClain, D. A. Protein modification by O-linked GlcNAc reduces angiogenesis by inhibiting Akt activity in endothelial cells. Arterioscler. Thromb. Vasc. Biol. 28, 651-657 (2008).
44. Dluhy, R. G. & McMahon, G. T. Intensive glycemic control in the ACCORD and ADVANCE trials. N. Engl. J. Med. 358, 2630-2633 (2008).
45. Lemons, J. M. et al. Quiescent fibroblasts exhibit high metabolic activity. PLoS Biol. 8, e1000514 (2010).
46. Pavlides, S. et al. Warburg meets autophagy: cancer-associated fibroblasts accelerate tumor growth and metastasis via oxidative stress, mitophagy, and aerobic glycolysis. Antioxid. Redox Signal. 16, 1264-1284 (2012).
47. Lisanti, M. P. et al. Understanding the ''lethal'' drivers of tumor-stroma coevolution: emerging role(s) for hypoxia, oxidative stress and autophagy/ mitophagy in the tumor micro-environment. Cancer Biol. Ther. 10, 537-542 (2010).
48. Chaudhri, V. K. et al. Metabolic alterations in lung cancer-associated fibroblasts correlated with increased glycolytic metabolism of the tumor. Mol. Cancer Res. 11, 579-592 (2013).
49. Santolla, M. F. et al. G protein-coupled estrogen receptor mediates the upregulation of fatty acid synthase induced by 17b-estradiol in cancer cells and cancer-associated fibroblasts. J. Biol. Chem. 287, 43234-43245 (2012).
50. Gajewski, T. F., Schreiber, H. & Fu, Y. X. Innate and adaptive immune cells in the tumor microenvironment. Nature Immunol. 14, 1014-1022 (2013).
51. Eheim, A., Medrikova, D. & Herzig, S. Immune cells and metabolic dysfunction. Semin. Immunopathol. 36, 13-25 (2014).
52. Jameson, S. C. & Masopust, D. Diversity in T cell memory: an embarrassment of riches. Immunity 31, 859-871 (2009).
53. Wahl, D. R., Byersdorfer, C. A., Ferrara, J. L., Opipari, A. W., Jr & Glick, G. D. Distinct metabolic programs in activated T cells: opportunities for selective immunomodulation. Immunol. Rev. 249, 104-115 (2012).
54. MacIver, N. J., Michalek, R. D. & Rathmell, J. C. Metabolic regulation of T lymphocytes. Annu. Rev. Immunol. 31, 259-283 (2013).
55. Pearce, E. L., Poffenberger, M. C., Chang, C. H. & Jones, R. G. Fueling immunity: insights into metabolism and lymphocyte function. Science 342, 1242454 (2013).
56. Jacobs, S. R. et al. Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways. J. Immunol. 180, 4476-4486 (2008).
57. Kaminski, M. M. et al. T cell activation is driven by anADP-dependent glucokinase linking enhanced glycolysis with mitochondrial reactive oxygen species generation. Cell Rep 2, 1300-1315 (2012).
58. Wang, R. et al. The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity 35, 871-882 (2011)
59. MacIver, N. J. et al. The liver kinase B1is a central regulator of T cell development, activation, and metabolism. J. Immunol. 187, 4187-4198 (2011).
60. Chang, C. H. et al. Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell 153, 1239-1251 (2013).
61. Cham, C. M., Driessens, G., O'Keefe, J. P. & Gajewski, T. F. Glucose deprivation inhibits multiple key gene expression events and effector functions in CD81 T cells. Eur. J. Immunol. 38, 2438-2450 (2008).
62. Sena, L. A. et al. Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling. Immunity 38, 225-236 (2013).
63. Metallo, C. M. et al. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 481, 380-384 (2012).
64. Wise, D. R. et al. Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of a-ketoglutarate to citrate to support cell growth and viability. Proc. Natl Acad. Sci. USA 108, 19611-19616 (2011).
65. Robichaud, P. P., Boulay, K., Munganyiki, J. E. & Surette, M. E. Fatty acid remodeling in cellular glycerophospholipids following the activation of human T cells. J. Lipid Res. 54, 2665-2677 (2013).
66. Shi, L. Z. et al. HIF1a-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J. Exp. Med. 208, 1367-1376 (2011).
67. Michalek, R. D. et al. Cutting edge: distinct glycolyticandlipid oxidativemetabolic programs are essential for effector and regulatory CD41 T cell subsets. J. Immunol. 186, 3299-3303 (2011).
68. Carr, E. L. et al. Glutamine uptake and metabolismare coordinately regulated by ERK/MAPK during T lymphocyte activation. J. Immunol. 185, 1037-1044 (2010).
69. Wang, R. & Green, D. R. Metabolic checkpoints in activated T cells. Nature Immunol. 13, 907-915 (2012).
70. Sundrud, M. S. et al. Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response. Science 324, 1334-1338 (2009).
71. van der Windt, G. J. et al. Mitochondrial respiratory capacity is a critical regulator of CD81 T cellmemory development. Immunity 36, 68-78 (2012).
72. Byersdorfer, C. A. et al. Effector T cells require fatty acid metabolism during murine graft-versus-host disease. Blood 122, 3230-3237 (2013).
73. Mantovani, A., Biswas, S. K., Galdiero, M. R., Sica, A. & Locati, M. Macrophage plasticity and polarization in tissue repair and remodelling. J. Pathol. 229, 176-185 (2013).
74. Rodríguez-Prados, J. C. et al. Substrate fate in activated macrophages: a comparison between innate, classic, and alternative activation. J. Immunol. 185, 605-614 (2010).
75. Nizet, V. & Johnson, R. S. Interdependence of hypoxic and innate immune responses. Nature Rev. Immunol. 9, 609-617 (2009).
76. Tannahill, G. M. et al. Succinate is an inflammatory signal that induces IL-1b through HIF-1a. Nature 496, 238-242 (2013).
77. Michelucci, A. et al. Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production. Proc. Natl Acad. Sci. USA 110, 7820-7825 (2013).
78. Hall, C. J. et al. Immunoresponsive gene 1 augments bactericidal activity of macrophage-lineage cells by regulating b-oxidation-dependent mitochondrial ROS production. Cell Metab. 18, 265-278 (2013).
79. O'Neill, L. A. A critical role for citrate metabolism in LPS signalling. Biochem. J. 438, e5-e6 (2011).
80. Ecker, J. et al. Induction of fatty acid synthesis is a key requirement for phagocytic differentiation of human monocytes. Proc. Natl Acad. Sci. USA 107, 7817-7822 (2010).
81. Vats, D. et al. Oxidative metabolism and PGC-1b attenuate macrophagemediated inflammation. Cell Metab. 4, 13-24 (2006).
82. O'Neill, L. A. & Hardie, D. G. Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature 493, 346-355 (2013).
83. Sene, A. et al. Impaired cholesterol efflux in senescent macrophages promotes age-related macular degeneration. Cell Metab. 17, 549-561 (2013).
84. Haschemi, A. et al. The sedoheptulose kinase CARKL directs macrophage polarization through control of glucose metabolism. Cell Metab. 15, 813-826 (2012).
85. Biswas, S. K. & Mantovani, A. Orchestration of metabolismby macrophages. Cell Metab. 15, 432-437 (2012).
86. Mills, C. D. M1 and M2 macrophages: oracles of health and disease. Crit. Rev. Immunol. 32, 463-488 (2012).
87. Popovic, P. J., Zeh, H. J. III & Ochoa, J. B. Arginine and immunity. J. Nutr. 137, 1681S-1686S (2007).
88. Sukumar, M. et al. Inhibiting glycolytic metabolism enhances CD81 T cell memory and antitumor function. J. Clin. Invest. 123, 4479-4488 (2013).
89. Arpaia, N. et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504, 451-455 (2013).
90. Furusawa, Y. et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446-450 (2013).
91. Smith, P. M. et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341, 569-573 (2013).
92. Sinclair, L. V. et al. Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation. Nature Immunol. 14, 500-508 (2013).
93. Telang, S. et al. Small molecule inhibition of 6-phosphofructo-2-kinase suppresses t cell activation. J. Transl. Med. 10, 95 (2012).
94. Clem, B. et al. Small-molecule inhibition of 6-phosphofructo-2-kinase activity suppresses glycolytic flux and tumor growth. Mol. Cancer Ther. 7, 110-120 (2008).
95. Obrosova, I. G. & Kador, P. F. Aldose reductase/polyol inhibitors for diabetic retinopathy. Curr. Pharm. Biotechnol. 12, 373-385 (2011).
96. Hotta, N., Kawamori, R., Fukuda, M., Shigeta, Y. & Aldose Reductase Inhibitor- Diabetes Complications Trial Study Group. Long-term clinical effects of epalrestat, an aldose reductase inhibitor, on progression of diabetic neuropathy and other microvascular complications: multivariate epidemiological analysis based on patient backgroundfactors and severity of diabetic neuropathy. Diabet. Med. 29, 1529-1533 (2012).
97. De Saedeleer, C. J. et al. Lactate activates HIF-1 in oxidative but not in Warburgphenotype human tumor cells. PLoS ONE 7, e46571 (2012).
98. Végran, F., Boidot, R., Michiels, C., Sonveaux, P. & Feron, O. Lactate influx through the endothelial cellmonocarboxylate transporterMCT1 supports an NF-kB/IL-8 pathway that drives tumor angiogenesis. Cancer Res. 71, 2550-2560 (2011).
99. Ruan, G. X. & Kazlauskas, A. Lactate engages receptor tyrosine kinases Axl, Tie2, and vascular endothelial growth factor receptor 2 to activate phosphoinositide 3-kinase/Akt and promote angiogenesis. J. Biol. Chem. 288, 21161-21172 (2013).
100. Wei, X. et al. De novo lipogenesis maintains vascular homeostasis through endothelial nitric-oxide synthase (eNOS) palmitoylation. J. Biol. Chem. 286, 2933-2945 (2011).
101. Majmundar, A. J., Wong, W. J. & Simon, M. C. Hypoxia-inducible factors and the response to hypoxic stress. Mol. Cell 40, 294-309 (2010).
102. Becker, J. C., Andersen, M. H., Schrama, D. & Thor Straten, P. Immunesuppressive properties of the tumor microenvironment. Cancer Immunol. Immunother. 62, 1137-1148 (2013).
103. Yan, Z., Garg, S. K., Kipnis, J. & Banerjee, R. Extracellular redox modulation by regulatory T cells. Nature Chem. Biol. 5, 721-723 (2009).
104. Yamanishi, S., Katsumura, K., Kobayashi, T. & Puro, D. G. Extracellular lactate as a dynamicvasoactive signal in the rat retinalmicrovasculature. Am. J. Physiol. Heart Circ. Physiol. 290, H925-H934 (2006).
105. Ohashi, T. et al. Dichloroacetate improves immune dysfunction caused by tumor-secreted lactic acid and increases antitumor immunoreactivity. Int. J. Cancer 133, 1107-1118 (2013).
106. Nieman, K. M. et al. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nature Med. 17, 1498-1503 (2011).