Metabolism in the Tumor Microenvironment

Literature Cited

1. Aiello NM, Bajor DL, Norgard RJ, Sahmoud A, Bhagwat N et al. 2016. Metastatic progression is associated with dynamic changes in the local microenvironment. Nat. Commun. 15:12819
   [Google Scholar]
2. Angelin A, Gil-de-Gómez L, Dahiya S, Jiao J, Guo L et al. 2017. Foxp3 reprograms T cell metabolism to function in low-glucose, high-lactate environments. Cell Metab 25:61282–87
   [Google Scholar]
3. Ardawi MSM, Newsholme EA. 1983. Glutamine metabolism in lymphocytes of the rat. Biochem. J. 212:3835–42
   [Google Scholar]
4. Auciello FR, Bulusu V, Oon C, Tait-Mulder J, Berry M et al. 2019. A stromal lysolipid-autotaxin signaling axis promotes pancreatic tumor progression. Cancer Discov 9:617–27
   [Google Scholar]
5. Bellon G, Monboisee J-C, Randoux A, Borel J-P 1987. Effects of preformed proline and proline amino acid precursors (including glutamine) on collagen synthesis in human fibroblast cultures. Biochim. Biophys. Acta 930:139–47
   [Google Scholar]
6. Berenbaum MC, Cope WA, Jeffery W 1973. Differential asparaginase sensitivity of T-cell and B-cell responses. Clin. Exp. Immunol. 15:4565–72
   [Google Scholar]
7. Biancur DE, Paulo JA, Małachowska B, Quiles Del Rey M, Sousa CM et al. 2017. Compensatory metabolic networks in pancreatic cancers upon perturbation of glutamine metabolism. Nat. Commun. 8:15965
   [Google Scholar]
8. Bingle L, Brown NJ, Lewis CE 2002. The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J. Pathol. 196:3254–65
   [Google Scholar]
9. Boj SF, Hwang C-I, Baker LA, Chio IIC, Engle DD et al. 2015. Organoid models of human and mouse ductal pancreatic cancer. Cell 160:1–2324–38
   [Google Scholar]
10. Bonuccelli G, Whitaker-Menezes D, Castello-Cros R, Pavlides S, Pestell RG et al. 2010. The reverse Warburg Effect: Glycolysis inhibitors prevent the tumor promoting effects of caveolin-1 deficient cancer associated fibroblasts. Cell Cycle 9:101960–71
    [Google Scholar]
11. Brand A, Singer K, Koehl GE, Kolitzus M, Schoenhammer G et al. 2016. LDHa-associated lactic acid production blunts tumor immunosurveillance by T and NK cells. Cell Metab 24:5657–71
    [Google Scholar]
12. Brand K, Aichinger S, Forster S, Kupper S, Neumann B et al. 1988. Cell-cycle-related metabolic and enzymatic events in proliferating rat thymocytes. Eur. J. Biochem. 172:3695–702
    [Google Scholar]
13. Breul SD, Bradley KH, Hance AJ, Schafer MP, Berg RA, Crystal RG 1980. Control of collagen production by human diploid lung fibroblasts. J. Biol. Chem. 255:115250–60
    [Google Scholar]
14. Buchman VM, Belyanchikova NI, Mkheidze DM, Litovchenko TA, Lichinitser MR et al. 1979. 2′-Deoxycytidine hydrochloride protection of mice against the lethal toxicity of cytosine arabinoside. Cancer Chemother. Pharmacol. 3:4229–34
    [Google Scholar]
15. Buescher JM, Antoniewicz MR, Boros LG, Burgess SC, Brunengraber H et al. 2015. A roadmap for interpreting ¹³C metabolite labeling patterns from cells. Curr. Opin. Biotechnol. 34:189–201
    [Google Scholar]
16. Burgess EA, Sylvén B. 1962. Glucose, lactate, and lactic dehydrogenase activity in normal interstitial fluid and that of solid mouse tumors. Cancer Res 22:581–88
    [Google Scholar]
17. Bynigeri RR, Jakkampudi A, Jangala R, Subramanyam C, Sasikala M et al. 2017. Pancreatic stellate cell: Pandora's box for pancreatic disease biology. World J. Gastroenterol. 23:3382–405
    [Google Scholar]
18. Cameron ML, Granger DL, Weinberg JB, Kozumbo WJ, Koren HS 1990. Human alveolar and peritoneal macrophages mediate fungistasis independently of l-arginine oxidation to nitrite or nitrate. Am. Rev. Respir. Dis. 142:1313–19
    [Google Scholar]
19. Camps JL, Chang SM, Hsu TC, Freeman MR, Hong SJ et al. 1990. Fibroblast-mediated acceleration of human epithelial tumor growth in vivo. PNAS 87:175–79
    [Google Scholar]
20. Cantor JR, Abu-Remaileh M, Kanarek N, Freinkman E, Gao X et al. 2017. Physiologic medium rewires cellular metabolism and reveals uric acid as an endogenous inhibitor of UMP synthase. Cell 169:2258–72.e17
    [Google Scholar]
21. Cham CM, Driessens G, O'Keefe JP, Gajewski TF 2008. Glucose deprivation inhibits multiple key gene expression events and effector functions in CD8⁺ T cells. Eur. J. Immunol. 38:92438–50
    [Google Scholar]
22. Cham CM, Gajewski TF. 2005. Glucose availability regulates IFN-γ production and p70S6 kinase activation in CD8⁺ effector T cells. J. Immunol. 174:84670–77
    [Google Scholar]
23. Chan T-S, Lakhchaura BD. 1982. Deoxycytidine excretion by mouse peritoneal macrophages: its implication in modulation of immunological functions. J. Cell. Physiol. 111:128–32
    [Google Scholar]
24. Chan TS, Lakhchaura BD, Hsu TF 1983. Differences in deoxycytidine metabolism in mouse and rat. Biochem. J. 210:2367–71
    [Google Scholar]
25. Chang C-H, Curtis JD, Maggi LB, Faubert B, Villarino AV et al. 2013. Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell 153:61239–51
    [Google Scholar]
26. Chang C-H, Qiu J, O'Sullivan D, Buck MD, Noguchi T et al. 2015. Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell 162:61229–41
    [Google Scholar]
27. Chang C-I, Liao JC, Kuo L 2001. Macrophage arginase promotes tumor cell growth and suppresses nitric oxide-mediated tumor cytotoxicity. Cancer Res 61:31100–6
    [Google Scholar]
28. Chen Q, Zhang XH-F, Massagué J 2011. Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs. Cancer Cell 20:4538–49
    [Google Scholar]
29. Chittezhath M, Dhillon MK, Lim JY, Laoui D, Shalova IN et al. 2014. Molecular profiling reveals a tumor-promoting phenotype of monocytes and macrophages in human cancer progression. Immunity 41:5815–29
    [Google Scholar]
30. Colegio OR, Chu N-Q, Szabo AL, Chu T, Rhebergen AM et al. 2014. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature 513:7519559–63
    [Google Scholar]
31. Coles NW, Johnstone RM. 1962. Glutamine metabolism in Ehrlich ascites-carcinoma cells. Biochem. J. 83:2284–91
    [Google Scholar]
32. Cori CF, Cori GT. 1925. The carbohydrate metabolism of tumors. II. Changes in the sugar, lactic acid, and CO₂-combining power of blood passing through a tumor. J. Biol. Chem. 65:2397–405
    [Google Scholar]
33. Costa A, Kieffer Y, Scholer-Dahirel A, Pelon F, Bourachot B et al. 2018. Fibroblast heterogeneity and immunosuppressive environment in human breast cancer. Cancer Cell 33:3463–79.e10
    [Google Scholar]
34. Costea DE, Hills A, Osman AH, Thurlow J, Kalna G et al. 2013. Identification of two distinct carcinoma-associated fibroblast subtypes with differential tumor-promoting abilities in oral squamous cell carcinoma. Cancer Res 73:133888–901
    [Google Scholar]
35. Dalin S, Sullivan MR, Lau AN, Grauman-Boss B, Mueller HSet al. 2019. Deoxycytidine release from pancreatic stellate cells promotes gemcitabine resistance. Cancer Res In press
36. Davidson SM, Jonas O, Keibler MA, Hou HW, Luengo A et al. 2017. Direct evidence for cancer-cell-autonomous extracellular protein catabolism in pancreatic tumors. Nat. Med. 23:2235–41
    [Google Scholar]
37. Davidson SM, Papagiannakopoulos T, Olenchock BA, Heyman JE, Keibler MA et al. 2016. Environment impacts the metabolic dependencies of Ras-driven non-small cell lung cancer. Cell Metab 23:3517–28
    [Google Scholar]
38. De Bock K, Georgiadou M, Carmeliet P 2013a. Role of endothelial cell metabolism in vessel sprouting. Cell Metab 18:5634–47
    [Google Scholar]
39. De Bock K, Georgiadou M, Schoors S, Kuchnio A, Wong BW et al. 2013b. Role of PFKFB3-driven glycolysis in vessel sprouting. Cell 154:3651–63
    [Google Scholar]
40. Deberardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M et al. 2007. Beyond aerobic glycolysis: Transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. PNAS 104:4919345–50
    [Google Scholar]
41. Delage B, Fennell DA, Nicholson L, McNeish I, Lemoine NR et al. 2010. Arginine deprivation and argininosuccinate synthetase expression in the treatment of cancer. Int. J. Cancer 126:122762–72
    [Google Scholar]
42. Denis M. 1991. Tumor necrosis factor and granulocyte macrophage-colony stimulating factor stimulate human macrophages to restrict growth of virulent Mycobacterium avium and to kill avirulent M. avium: killing effector mechanism depends on the generation of reactive nitrogen intermediates. J. Leukoc. Biol. 49:4380–87
    [Google Scholar]
43. Derlindati E, Dei Cas A, Montanini B, Spigoni V, Curella V et al. 2015. Transcriptomic analysis of human polarized macrophages: More than one role of alternative activation?. PLOS ONE 10:3e0119751
    [Google Scholar]
44. Diebold LP, Gil HJ, Gao P, Martinez CA, Weinberg SE, Chandel NS 2019. Mitochondrial complex III is necessary for endothelial cell proliferation during angiogenesis. Nat. Metab. 1:1158–71
    [Google Scholar]
45. Divakaruni AS, Hsieh WY, Minarrieta L, Duong TN, Kim KKO et al. 2018. Etomoxir inhibits macrophage polarization by disrupting CoA homeostasis. Cell Metab 28:3490–503.e7
    [Google Scholar]
46. Dorresteijn MJ, Paine A, Zilian E, Fenten MGE, Frenzel E et al. 2015. Cell-type-specific downregulation of heme oxygenase-1 by lipopolysaccharide via Bach1 in primary human mononuclear cells. Free Radic. Biol. Med. 78:224–32
    [Google Scholar]
47. Downes CS, Johnson RT, Yew FF 1983. Effects of conditioned medium on nucleoside uptake, cell cycle progression and apparent DNA repair. J. Cell Sci. 59:1145–58
    [Google Scholar]
48. Dudley AC. 2012. Tumor endothelial cells. Cold Spring Harb. Perspect. Med. 2:3a006536
    [Google Scholar]
49. Ebos JML, Kerbel RS. 2011. Antiangiogenic therapy: impact on invasion, disease progression, and metastasis. Nat. Rev. Clin. Oncol. 8:4210–21
    [Google Scholar]
50. Eccles SA, Alexander P. 1974. Macrophage content of tumours in relation to metastatic spread and host immune reaction. Nature 250:5468667–69
    [Google Scholar]
51. Fan TWM, Lane AN, Higashi RM 2016. Stable isotope resolved metabolomics studies in ex vivo tissue slices. Bio Protoc 6:3e1730
    [Google Scholar]
52. Faubert B, Li KY, Cai L, Hensley CT, Kim J et al. 2017. Lactate metabolism in human lung tumors. Cell 171:2358–59
    [Google Scholar]
53. Feig C, Gopinathan A, Neesse A, Chan DS, Cook N, Tuveson DA 2012. The pancreas cancer microenvironment. Clin. Cancer Res. 18:164266–76
    [Google Scholar]
54. Fidler IJ. 1974. Inhibition of pulmonary metastasis by intravenous injection of specifically activated macrophages. Cancer Res 34:51074–78
    [Google Scholar]
55. Finerman GA, Downing S, Rosenberg LE 1967. Amino acid transport in bone. II. Regulation of collagen synthesis by perturbation of proline transport. Biochim. Biophys. Acta 135:51008–15
    [Google Scholar]
56. Folkman J. 1971. Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 285:211182–86
    [Google Scholar]
57. Francescone R, Vendramini-Costa DB, Franco-Barraza J, Wagner J, Muir A et al. 2018. NetrinG1/NGL-1 axis promotes pancreatic tumorigenesis through cancer associated fibroblast derived nutritional supply and immunosuppression. bioRxiv 330209. https://doi.org/10.1101/330209
    [Crossref]
58. Franco-Barraza J, Francescone R, Luong T, Shah N, Madhani R et al. 2017. Matrix-regulated integrin α_vβ₅ maintains α₅β₁-dependent desmoplastic traits prognostic of neoplastic recurrence. eLife 6:e20600
    [Google Scholar]
59. Frauwirth KA, Riley JL, Harris MH, Parry RV, Rathmell JC et al. 2002. The CD28 signaling pathway regulates glucose metabolism. Immunity 16:6769–77
    [Google Scholar]
60. Geiger R, Rieckmann JC, Wolf T, Basso C, Feng Y et al. 2016. l-Arginine modulates T cell metabolism and enhances survival and anti-tumor activity. Cell 167:3829–42.e13
    [Google Scholar]
61. Gerriets VA, Kishton RJ, Johnson MO, Cohen S, Siska PJ et al. 2016. Foxp3 and Toll-like receptor signaling balance T_reg cell anabolic metabolism for suppression. Nat. Immunol. 17:1459–66
    [Google Scholar]
62. Gleave M, Hsieh J-T, Gao C, von Eschenbach AC, Chung LWK 1991. Acceleration of human prostate cancer growth in vivo by factors produced by prostate and bone fibroblasts. Cancer Res 51:143753–61
    [Google Scholar]
63. Green H, Goldberg B. 1965. Synthesis of collagen by mammalian cell lines of fibroblastic and nonfibroblastic origin. PNAS 53:61360–65
    [Google Scholar]
64. Gullino PM, Clark SH, Grantham FH 1964. The interstitial fluid of solid tumors. Cancer Res 24:5780–97
    [Google Scholar]
65. Halama A, Guerrouahen BS, Pasquier J, Satheesh NJ, Suhre K, Rafii A 2017. Nesting of colon and ovarian cancer cells in the endothelial niche is associated with alterations in glycan and lipid metabolism. Sci. Rep. 7:39999
    [Google Scholar]
66. Halbrook CJ, Pontious C, Kovalenko I, Lapienyte L, Dreyer S et al. 2019. Macrophage-released pyrimidines inhibit gemcitabine therapy in pancreatic cancer. Cell Metab 29:61390–99.e6
    [Google Scholar]
67. Hamanaka RB, Nigdelioglu R, Meliton AY, Tian Y, Witt LJ et al. 2018. Inhibition of phosphoglycerate dehydrogenase attenuates bleomycin-induced pulmonary fibrosis. Am. J. Respir. Cell Mol. Biol. 58:5585–93
    [Google Scholar]
68. Hensley CT, Faubert B, Yuan Q, Lev-Cohain N, Jin E et al. 2016. Metabolic heterogeneity in human lung tumors. Cell 164:4681–94
    [Google Scholar]
69. Hessmann E, Patzak MS, Klein L, Chen N, Kari V et al. 2018. Fibroblast drug scavenging increases intratumoural gemcitabine accumulation in murine pancreas cancer. Gut 67:3497–507
    [Google Scholar]
70. Hibbs JB, Taintor RR, Vavrin Z, Rachlin EM 1988. Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem. Biophys. Res. Commun. 157:187–94
    [Google Scholar]
71. Ho P-C, Bihuniak JD, Macintyre AN, Staron M, Liu X et al. 2015. Phosphoenolpyruvate is a metabolic checkpoint of anti-tumor T cell responses. Cell 162:61217–28
    [Google Scholar]
72. Hosios AM, Hecht VC, Danai LV, Johnson MO, Rathmell JC et al. 2016. Amino acids rather than glucose account for the majority of cell mass in proliferating mammalian cells. Dev. Cell. 36:5540–49
    [Google Scholar]
73. Howie D, Cobbold SP, Adams E, Ten Bokum A, Necula AS et al. 2017. Foxp3 drives oxidative phosphorylation and protection from lipotoxicity. JCI Insight 2:3e89160
    [Google Scholar]
74. Huang H, Vandekeere S, Kalucka J, Bierhansl L, Zecchin A et al. 2017. Role of glutamine and interlinked asparagine metabolism in vessel formation. EMBO J 36:162334–52
    [Google Scholar]
75. Huang L, Holtzinger A, Jagan I, BeGora M, Lohse I et al. 2015. Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell- and patient-derived tumor organoids. Nat. Med. 21:111364–71
    [Google Scholar]
76. Huang SC-C, Everts B, Ivanova Y, O'Sullivan D, Nascimento M et al. 2014. Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. Nat. Immunol. 15:9846–55
    [Google Scholar]
77. Hui S, Ghergurovich JM, Morscher RJ, Jang C, Teng X et al. 2017. Glucose feeds the TCA cycle via circulating lactate. Nature 551:7678115–18
    [Google Scholar]
78. Hynds RE, Vladimirou E, Janes SM 2018. The secret lives of cancer cell lines. Dis. Models Mech. 11:11dmm037366
    [Google Scholar]
79. Jacobetz MA, Chan DS, Neesse A, Bapiro TE, Cook N et al. 2013. Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut 62:1112–20
    [Google Scholar]
80. Jacobs SR, Herman CE, MacIver NJ, Wofford JA, Wieman HL et al. 2008. Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways. J. Immunol. 180:74476–86
    [Google Scholar]
81. Jha AK, Huang SC-C, Sergushichev A, Lampropoulou V, Ivanova Y et al. 2015. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity 42:3419–30
    [Google Scholar]
82. Joyce JA, Fearon DT. 2015. T cell exclusion, immune privilege, and the tumor microenvironment. Science 348:623074–80
    [Google Scholar]
83. Kalluri R. 2016. The biology and function of fibroblasts in cancer. Nat. Rev. Cancer 16:9582–98
    [Google Scholar]
84. Kamine J, Rubin H. 1977. Coordinate control of collagen synthesis and cell growth in chick embryo fibroblasts and the effect of viral transformation on collagen synthesis. J. Cell. Physiol. 92:11–11
    [Google Scholar]
85. Katheder NS, Khezri R, O'Farrell F, Schultz SW, Jain A et al. 2017. Microenvironmental autophagy promotes tumour growth. Nature 541:7637417–20
    [Google Scholar]
86. Kershenobich D, Fierro FJ, Rojkind M 1970. The relationship between the free pool of proline and collagen content in human liver cirrhosis. J. Clin. Investig. 49:122246–49
    [Google Scholar]
87. Kim EJ, Sahai V, Abel EV, Griffith KA, Greenson JK et al. 2014. Pilot clinical trial of hedgehog pathway inhibitor GDC-0449 (vismodegib) in combination with gemcitabine in patients with metastatic pancreatic adenocarcinoma. Clin. Cancer Res. 20:235937–45
    [Google Scholar]
88. Knudsen ES, Balaji U, Freinkman E, McCue P, Witkiewicz AK 2016. Unique metabolic features of pancreatic cancer stroma: relevance to the tumor compartment, prognosis, and invasive potential. Oncotarget 7:4878396–411
    [Google Scholar]
89. Ko J-H, Imprialou M, Bagnati M, Srivastava PK, Vu HA et al. 2017. BCAT1 controls metabolic reprogramming in activated human macrophages and is associated with inflammatory diseases. Nat. Commun. 8:16040
    [Google Scholar]
90. Kobayashi M, Jeschke MG, Shigematsu K, Asai A, Yoshida S et al. 2010. M2b monocytes predominated in peripheral blood of severely burned patients. J. Immunol. 185:127174–79
    [Google Scholar]
91. Lampropoulou V, Sergushichev A, Bambouskova M, Nair S, Vincent EE et al. 2016. Itaconate links inhibition of succinate dehydrogenase with macrophage metabolic remodeling and regulation of inflammation. Cell Metab 24:1158–66
    [Google Scholar]
92. Lavin Y, Winter D, Blecher-Gonen R, David E, Keren-Shaul H et al. 2014. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 159:61312–26
    [Google Scholar]
93. Lee CGL, Jenkins NA, Gilbert DJ, Copeland NG, O'Brien WE 1995. Cloning and analysis of gene regulation of a novel LPS-inducible cDNA. Immunogenetics 41:5263–70
    [Google Scholar]
94. Lee JJ, Perera RM, Wang H, Wu D-C, Liu XS et al. 2014. Stromal response to Hedgehog signaling restrains pancreatic cancer progression. PNAS 111:30E3091–100
    [Google Scholar]
95. Lehtinen P, Takala I, Kulonen E 1978. Dependence of collagen synthesis by embryonic chick tendon cells on the extracellular concentrations of glutamine. Connect. Tissue Res. 6:3155–59
    [Google Scholar]
96. Lemons JMS, Feng X-J, Bennett BD, Legesse-Miller A, Johnson EL et al. 2010. Quiescent fibroblasts exhibit high metabolic activity. PLOS Biol 8:10e1000514
    [Google Scholar]
97. Li X, Nadauld L, Ootani A, Corney DC, Pai RK et al. 2014. Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture. Nat. Med. 20:7769–77
    [Google Scholar]
98. Lin EY, Nguyen AV, Russell RG, Pollard JW 2001. Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J. Exp. Med. 193:6727–40
    [Google Scholar]
99. Linares JF, Cordes T, Duran A, Reina-Campos M, Valencia T et al. 2017. ATF4-induced metabolic reprograming is a synthetic vulnerability of the p62-deficient tumor stroma. Cell Metab 26:6817–29.e6
    [Google Scholar]
100. Liotta LA, Gattozzi C, Kleinerman J, Saidel G 1977. Reduction of tumour cell entry into vessels by BCG-activated macrophages. Br. J. Cancer 36:5639–41
     [Google Scholar]
101. Liu D, Chang C, Lu N, Wang X, Lu Q et al. 2017. Comprehensive proteomics analysis reveals metabolic reprogramming of tumor-associated macrophages stimulated by the tumor microenvironment. J. Proteome Res. 16:1288–97
     [Google Scholar]
102. Llufrio EM, Wang L, Naser FJ, Patti GJ 2018. Sorting cells alters their redox state and cellular metabolome. Redox Biol 16:381–87
     [Google Scholar]
103. Ma EH, Bantug G, Griss T, Condotta S, Johnson RM et al. 2017. Serine is an essential metabolite for effector T cell expansion. Cell Metab 25:2345–57
     [Google Scholar]
104. MacIver NJ, Jacobs SR, Wieman HL, Wofford JA, Coloff JL, Rathmell JC 2008. Glucose metabolism in lymphocytes is a regulated process with significant effects on immune cell function and survival. J. Leukoc. Biol. 84:4949–57
     [Google Scholar]
105. Maishi N, Ohba Y, Akiyama K, Ohga N, Hamada J-I et al. 2016. Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan. Sci. Rep. 6:28039
     [Google Scholar]
106. Maj T, Wang W, Crespo J, Zhang H, Wang W et al. 2017. Oxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumor. Nat. Immunol. 18:121332–41
     [Google Scholar]
107. Marletta MA, Yoon PS, Iyengar R, Leaf CD, Wishnok JS 1988. Macrophage oxidation of l-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry 27:248706–11
     [Google Scholar]
108. Mayers JR, Vander Heiden MG 2015. Famine versus feast: understanding the metabolism of tumors in vivo. Trends Biochem. Sci. 40:3130–40
     [Google Scholar]
109. McFadden BA, Purohit S. 1977. Itaconate, an isocitrate lyase-directed inhibitor in Pseudomonas indigofera. J. Bacteriol. 131:1136–44
     [Google Scholar]
110. Michalek RD, Rathmell JC. 2010. The metabolic life and times of a T-cell. Immunol. Rev. 236:1190–202
     [Google Scholar]
111. Michelucci A, Cordes T, Ghelfi J, Pailot A, Reiling N et al. 2013. Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production. PNAS 110:197820–25
     [Google Scholar]
112. Migneco G, Whitaker-Menezes D, Chiavarina B, Castello-Cros R, Pavlides S et al. 2010. Glycolytic cancer associated fibroblasts promote breast cancer tumor growth, without a measurable increase in angiogenesis: evidence for stromal-epithelial metabolic coupling. Cell Cycle 9:122412–22
     [Google Scholar]
113. Miller-Fleming L, Olin-Sandoval V, Campbell K, Ralser M 2015. Remaining mysteries of molecular biology: the role of polyamines in the cell. J. Mol. Biol. 427:213389–406
     [Google Scholar]
114. Mills EL, Ryan DG, Prag HA, Dikovskaya D, Menon D et al. 2018. Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature 556:7699113–17
     [Google Scholar]
115. Moffett JR, Namboodiri MA. 2003. Tryptophan and the immune response. Immunol. Cell Biol. 81:4247–65
     [Google Scholar]
116. Muir A, Danai LV, Gui DY, Waingarten CY, Lewis CA, Vander Heiden MG 2017. Environmental cystine drives glutamine anaplerosis and sensitizes cancer cells to glutaminase inhibition. eLife 6:e27713
     [Google Scholar]
117. Muir A, Danai LV, Vander Heiden MG 2018. Microenvironmental regulation of cancer cell metabolism: implications for experimental design and translational studies. Dis. Models Mech. 11:8dmm035758
     [Google Scholar]
118. Munder M, Mollinedo F, Calafat J, Canchado J, Gil-Lamaignere C et al. 2005. Arginase I is constitutively expressed in human granulocytes and participates in fungicidal activity. Blood 105:62549–56
     [Google Scholar]
119. Muranen T, Iwanicki MP, Curry NL, Hwang J, DuBois CD et al. 2017. Starved epithelial cells uptake extracellular matrix for survival. Nat. Commun. 8:13989
     [Google Scholar]
120. Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW et al. 2014. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 41:114–20
     [Google Scholar]
121. Namgaladze D, Brüne B. 2014. Fatty acid oxidation is dispensable for human macrophage IL-4-induced polarization. Biochim. Biophys. Acta 1841:91329–35
     [Google Scholar]
122. Neesse A, Frese KK, Bapiro TE, Nakagawa T, Sternlicht MD et al. 2013. CTGF antagonism with mAb FG-3019 enhances chemotherapy response without increasing drug delivery in murine ductal pancreas cancer. PNAS 110:3012325–30
     [Google Scholar]
123. Newsholme P, Curi R, Gordon S, Newsholme EA 1986. Metabolism of glucose, glutamine, long-chain fatty acids and ketone bodies by murine macrophages. Biochem. J. 239:1121–25
     [Google Scholar]
124. Newsholme P, Gordon S, Newsholme EA 1987. Rates of utilization and fates of glucose, glutamine, pyruvate, fatty acids and ketone bodies by mouse macrophages. Biochem. J. 242:3631–36
     [Google Scholar]
125. Nicholson S, Bonecini-Almeida MG, Lapa e Silva JR, Nathan C, Xie QW et al. 1996. Inducible nitric oxide synthase in pulmonary alveolar macrophages from patients with tuberculosis. J. Exp. Med. 183:52293–302
     [Google Scholar]
126. Nigdelioglu R, Hamanaka RB, Meliton AY, O'Leary E, Witt LJ et al. 2016. Transforming growth factor (TGF)-β promotes de novo serine synthesis for collagen production. J. Biol. Chem. 291:5327239–51
     [Google Scholar]
127. Nomura M, Liu J, Rovira II, Gonzalez-Hurtado E, Lee J et al. 2016. Fatty acid oxidation in macrophage polarization. Nat. Immunol. 17:3216–17
     [Google Scholar]
128. Ochocki JD, Khare S, Hess M, Ackerman D, Qiu B et al. 2018. Arginase 2 suppresses renal carcinoma progression via biosynthetic cofactor pyridoxal phosphate depletion and increased polyamine toxicity. Cell Metab 27:61263–66
     [Google Scholar]
129. O'Connor RS, Guo L, Ghassemi S, Snyder NW, Worth AJ et al. 2018. The CPT1a inhibitor, etomoxir induces severe oxidative stress at commonly used concentrations. Sci. Rep. 8:16289
     [Google Scholar]
130. Ohnuma T, Holland JF, Arkin H, Minowada J 1977. l-Asparagine requirements of human T-lymphocytes and B-lymphocytes in culture. J. Natl. Cancer Inst. 59:41061–63
     [Google Scholar]
131. Olivares O, Mayers JR, Gouirand V, Torrence ME, Gicquel T et al. 2017. Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions. Nat. Commun. 8:16031
     [Google Scholar]
132. Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D et al. 2009. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 324:59331457–61
     [Google Scholar]
133. Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, Cunha GR 1999. Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res 59:195002–11
     [Google Scholar]
134. Öhlund D, Handly-Santana A, Biffi G, Elyada E, Almeida AS et al. 2017. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J. Exp. Med. 7:579–96
     [Google Scholar]
135. Özdemir BC, Pentcheva-Hoang T, Carstens JL, Zheng X, Wu C-C et al. 2014. Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell 25:6719–34
     [Google Scholar]
136. Palmieri EM, Menga A, Martín-Pérez R, Quinto A, Riera-Domingo C et al. 2017. Pharmacologic or genetic targeting of glutamine synthetase skews macrophages toward an M1-like phenotype and inhibits tumor metastasis. Cell Rep 20:71654–66
     [Google Scholar]
137. Patel TR, McFadden BA. 1978. Caenorhabditis elegans and Ascaris suum: inhibition of isocitrate lyase by itaconate. Exp. Parasitol. 44:2262–68
     [Google Scholar]
138. Pavlides S, Vera I, Gandara R, Sneddon S, Pestell RG et al. 2012. Warburg meets autophagy: cancer-associated fibroblasts accelerate tumor growth and metastasis via oxidative stress, mitophagy, and aerobic glycolysis. Antioxid. Redox Signal. 16:111264–84
     [Google Scholar]
139. Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK et al. 2009. The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle 8:233984–4001
     [Google Scholar]
140. Pesce JT, Ramalingam TR, Mentink-Kane MM, Wilson MS, El Kasmi KC et al. 2009. Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis. PLOS Pathog 5:4e1000371
     [Google Scholar]
141. Phang JM, Finerman GA, Singh B, Rosenberg LE, Berman M 1971. Compartmental analysis of collagen synthesis in fetal rat calvaria. I. Perturbations proline transport. Biochim. Biophys. Acta 230:1146–59
     [Google Scholar]
142. Picard O, Rolland Y, Poupon MF 1986. Fibroblast-dependent tumorigenicity of cells in nude mice: implication for implantation of metastases. Cancer Res 46:73290–94
     [Google Scholar]
143. Poillet-Perez L, Xie X, Zhan L, Yang Y, Sharp DW et al. 2018. Autophagy maintains tumour growth through circulating arginine. Nature 563:7732569–73
     [Google Scholar]
144. Porporato PE, Payen VL, De Saedeleer CJ, Préat V, Thissen J-P et al. 2012. Lactate stimulates angiogenesis and accelerates the healing of superficial and ischemic wounds in mice. Angiogenesis 15:4581–92
     [Google Scholar]
145. Priest RE, Davies LM. 1969. Cellular proliferation and synthesis of collagen. Lab. Investig. 21:2138–42
     [Google Scholar]
146. Pritchett TR, Wang JKM, Jones PA 1989. Mesenchymal-epithelial interactions between normal and transformed human bladder cells. Cancer Res 49:102750–54
     [Google Scholar]
147. Provenzano PP, Cuevas C, Chang AE, Goel VK, von Hoff DD, Hingorani SR 2012. Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell 21:3418–29
     [Google Scholar]
148. Pyonteck SM, Gadea BB, Wang H-W, Gocheva V, Hunter KE et al. 2012. Deficiency of the macrophage growth factor CSF-1 disrupts pancreatic neuroendocrine tumor development. Oncogene 31:111459–67
     [Google Scholar]
149. Rabinovitz M, Olson ME, Greenberg DM 1956. Role of glutamine in protein synthesis by the Ehrlich ascites carcinoma. J. Biol. Chem. 222:2879–93
     [Google Scholar]
150. Racker E, Resnick RJ, Feldman R 1985. Glycolysis and methylaminoisobutyrate uptake in rat-1 cells transfected with ras or myc oncogenes. PNAS 82:113535–38
     [Google Scholar]
151. Rae C, Nasrallah FA, Bröer S 2009. Metabolic effects of blocking lactate transport in brain cortical tissue slices using an inhibitor specific to MCT1 and MCT2. Neurochem. Res. 34:101783–91
     [Google Scholar]
152. Raes G, Brys L, Dahal BK, Brandt J, Grooten J et al. 2005. Macrophage galactose-type C-type lectins as novel markers for alternatively activated macrophages elicited by parasitic infections and allergic airway inflammation. J. Leukoc. Biol. 77:3321–27
     [Google Scholar]
153. Ramanathan RK, McDonough SL, Philip PA, Hingorani SR, Lacy J et al. 2019. Phase IB/II randomized study of FOLFIRINOX plus pegylated recombinant human hyaluronidase versus FOLFIRINOX alone in patients with metastatic pancreatic adenocarcinoma: SWOG S1313. J. Clin. Oncol. 37:131062–69
     [Google Scholar]
154. Ramjiawan RR, Griffioen AW, Duda DG 2017. Anti-angiogenesis for cancer revisited: Is there a role for combinations with immunotherapy?. Angiogenesis 20:2185–204
     [Google Scholar]
155. Raud B, Roy DG, Divakaruni AS, Tarasenko TN, Franke R et al. 2018. Etomoxir actions on regulatory and memory T cells are independent of Cpt1a-mediated fatty acid oxidation. Cell Metab 28:3504–7
     [Google Scholar]
156. Reitzer LJ, Wice BM, Kennell D 1979. Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells. J. Biol. Chem. 254:82669–76
     [Google Scholar]
157. Rhim AD, Oberstein PE, Thomas DH, Mirek ET, Palermo CF et al. 2014. Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell 25:6735–47
     [Google Scholar]
158. Rodriguez PC, Quiceno DG, Zabaleta J, Ortiz B, Zea AH et al. 2004. Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-Cell receptor expression and antigen-specific T-cell responses. Cancer Res 64:165839–49
     [Google Scholar]
159. Rodríguez-Prados J-C, Través PG, Cuenca J, Rico D, Aragonés J et al. 2010. Substrate fate in activated macrophages: a comparison between innate, classic, and alternative activation. J. Immunol. 185:1605–14
     [Google Scholar]
160. Rojkind M, Diaz de León L 1970. Collagen biosynthesis in cirrhotic rat liver slices: a regulatory mechanism. Biochim. Biophys. Acta 217:2512–22
     [Google Scholar]
161. Routy J-P, Routy B, Graziani GM, Mehraj V 2016. The kynurenine pathway is a double-edged sword in immune-privileged sites and in cancer: implications for immunotherapy. Int. J. Tryptophan Res. 9:67–77
     [Google Scholar]
162. Rouzaut A, Subirá ML, de Miguel C, Domingo-de-Miguel E, González A et al. 1999. Co-expression of inducible nitric oxide synthase and arginases in different human monocyte subsets. Apoptosis regulated by endogenous NO. Biochim. Biophys. Acta 1451:2319–33
     [Google Scholar]
163. Ruan G-X, Kazlauskas A. 2013. 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. 288:2921161–72
     [Google Scholar]
164. Scharping NE, Menk AV, Moreci RS, Whetstone RD, Dadey RE et al. 2016. The tumor microenvironment represses T cell mitochondrial biogenesis to drive intratumoral T cell metabolic insufficiency and dysfunction. Immunity 45:2374–88
     [Google Scholar]
165. Schnoor M, Cullen P, Lorkowski J, Stolle K, Robenek H et al. 2008. Production of type VI collagen by human macrophages: a new dimension in macrophage functional heterogeneity. J. Immunol. 180:85707–19
     [Google Scholar]
166. Schoors S, Bruning U, Missiaen R, Queiroz KCS, Borgers G et al. 2015. Fatty acid carbon is essential for dNTP synthesis in endothelial cells. Nature 520:7546192–97
     [Google Scholar]
167. Schreiber RD, Old LJ, Smyth MJ 2011. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science 331:60241565–70
     [Google Scholar]
168. Schrek R, Dolowy WC, Ammeraal RN 1967. l-asparaginase: toxicity to normal and leukemic human lymphocytes. Science 155:3760329–30
     [Google Scholar]
169. Schroder K, Irvine KM, Taylor MS, Bokil NJ, Le Cao KA et al. 2012. Conservation and divergence in Toll-like receptor 4-regulated gene expression in primary human versus mouse macrophages. PNAS 109:16E944–53
     [Google Scholar]
170. Sellers K, Fox MP, Bousamra M II, Slone SP, Higashi RM et al. 2015. Pyruvate carboxylase is critical for non-small-cell lung cancer proliferation. J. Clin. Investig. 125:2687–98
     [Google Scholar]
171. Shamir M, Bar-On Y, Phillips R, Milo R 2016. SnapShot: timescales in cell biology. Cell 164:61302.e1
     [Google Scholar]
172. Sherman MH, Yu RT, Engle DD, Ding N, Atkins AR et al. 2014. Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy. Cell 159:180–93
     [Google Scholar]
173. Shin J-H, Yang J-Y, Jeon B-Y, Yoon YJ, Cho S-N et al. 2011. ¹H NMR-based metabolomic profiling in mice infected with Mycobacterium tuberculosis. J. . Proteome Res 10:52238–47
     [Google Scholar]
174. Siska PJ, Beckermann KE, Mason FM, Andrejeva G, Greenplate AR et al. 2017. Mitochondrial dysregulation and glycolytic insufficiency functionally impair CD8 T cells infiltrating human renal cell carcinoma. JCI Insight 2:12e93411
     [Google Scholar]
175. Sousa CM, Biancur DE, Wang X, Halbrook CJ, Sherman MH et al. 2016. Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. Nature 536:7617479–83
     [Google Scholar]
176. Spinelli JB, Yoon H, Ringel AE, Jeanfavre S, Clish CB, Haigis MC 2017. Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass. Science 358:6365941–46
     [Google Scholar]
177. Strelko CL, Lu W, Dufort FJ, Seyfried TN, Chiles TC et al. 2011. Itaconic acid is a mammalian metabolite induced during macrophage activation. J. Am. Chem. Soc. 133:4116386–89
     [Google Scholar]
178. Su S, Chen J, Yao H, Liu J, Yu S et al. 2018. CD10⁺GPR77⁺ cancer-associated fibroblasts promote cancer formation and chemoresistance by sustaining cancer stemness. Cell 172:4841–56.e16
     [Google Scholar]
179. Su S, Liu Q, Chen J, Chen J, Chen F et al. 2014. A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis. Cancer Cell 25:5605–20
     [Google Scholar]
180. Sugimoto M, Sakagami H, Yokote Y, Onuma H, Kaneko M et al. 2012. Non-targeted metabolite profiling in activated macrophage secretion. Metabolomics 8:4624–33
     [Google Scholar]
181. Sullivan MR, Danai LV, Lewis CA, Chan SH, Gui DY et al. 2019. Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability. eLife 8e44235
182. Thomas AC. 2014. “Of mice and men”: arginine metabolism in macrophages. Front. Immunol. 5:479
     [Google Scholar]
183. Vaage J, Harlos JP. 1991. Collagen production by macrophages in tumour encapsulation and dormancy. Br. J. Cancer 63:5758–62
     [Google Scholar]
184. Valencia T, Kim JY, Abu-Baker S, Moscat-Pardos J, Ahn CS et al. 2014. Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis. Cancer Cell 26:1121–35
     [Google Scholar]
185. Van den Bossche J, Baardman J, Otto NA, van der Velden S, Neele AE et al. 2016. Mitochondrial dysfunction prevents repolarization of inflammatory macrophages. Cell Rep 17:3684–96
     [Google Scholar]
186. Vande Voorde J, Ackermann T, Pfetzer N, Sumpton D, MacKay G et al. 2019. Improving the metabolic fidelity of cancer models with a physiological cell culture medium. Sci. Adv. 5:1eaau7314
     [Google Scholar]
187. Vandekeere S, Dubois C, Kalucka J, Sullivan MR, García-Caballero M et al. 2018. Serine synthesis via PHGDH is essential for heme production in endothelial cells. Cell Metab 28:4573–87.e13
     [Google Scholar]
188. Vats D, Mukundan L, Odegaard JI, Zhang L, Smith KL et al. 2006. Oxidative metabolism and PGC-1β attenuate macrophage-mediated inflammation. Cell Metab 4:113–24
     [Google Scholar]
189. Vijayan V, Pradhan P, Braud L, Fuchs HR, Gueler F et al. 2019. Human and murine macrophages exhibit differential metabolic responses to lipopolysaccharide—a divergent role for glycolysis. Redox Biol 22:101147
     [Google Scholar]
190. Vincent AS, Phan TT, Mukhopadhyay A, Lim HY, Halliwell B, Wong KP 2008. Human skin keloid fibroblasts display bioenergetics of cancer cells. J. Investig. Dermatol. 128:3702–9
     [Google Scholar]
191. Walsh AJ, Castellanos JA, Nagathihalli NS, Merchant NB, Skala MC 2016. Optical imaging of drug-induced metabolism changes in murine and human pancreatic cancer organoids reveals heterogeneous drug response. Pancreas 45:6863–69
     [Google Scholar]
192. Wang T, Marquardt C, Foker J 1976. Aerobic glycolysis during lymphocyte proliferation. Nature 261:5562702–5
     [Google Scholar]
193. Warburg O. 1925. Über den Stoffwechsel der Carcinomzelle. Klin. Wochenschr. 4:12534–36
     [Google Scholar]
194. Warburg O, Wind F, Negelein E 1927. The metabolism of tumors in the body. J. Gen. Physiol. 8:6519–30
     [Google Scholar]
195. Watari N, Hotta Y, Mabuchi Y 1982. Morphological studies on a vitamin A-storing cell and its complex with macrophage observed in mouse pancreatic tissues following excess vitamin A administration TI. Okajimas Folia Anat. Jpn. 58:4–6837–57
     [Google Scholar]
196. Weinberg JB, Misukonis MA, Shami PJ, Mason SN, Sauls DL et al. 1995. Human mononuclear phagocyte inducible nitric oxide synthase (iNOS): analysis of iNOS mRNA, iNOS protein, biopterin, and nitric oxide production by blood monocytes and peritoneal macrophages. Blood 86:31184–95
     [Google Scholar]
197. Weinberg SE, Singer BD, Steinert EM, Martinez CA, Mehta MM et al. 2019. Mitochondrial complex III is essential for suppressive function of regulatory T cells. Nature 565:7740495–99
     [Google Scholar]
198. Weiss JM, Davies LC, Karwan M, Ileva L, Ozaki MK et al. 2018. Itaconic acid mediates crosstalk between macrophage metabolism and peritoneal tumors. J. Clin. Investig. 128:93794–805
     [Google Scholar]
199. Weitkamp B, Cullen P, Plenz G, Robenek H, Rauterberg J 1999. Human macrophages synthesize type VIII collagen in vitro and in the atherosclerotic plaque. FASEB J 13:111445–57
     [Google Scholar]
200. Wenes M, Shang M, Di Matteo M, Goveia J, Martín-Pérez R et al. 2016. Macrophage metabolism controls tumor blood vessel morphogenesis and metastasis. Cell Metab 24:5701–15
     [Google Scholar]
201. Whatcott CJ, Diep CH, Jiang P, Watanabe A, LoBello J et al. 2015. Desmoplasia in primary tumors and metastatic lesions of pancreatic cancer. Clin. Cancer Res. 21:153561–68
     [Google Scholar]
202. Whitaker-Menezes D, Martinez-Outschoorn UE, Lin Z, Ertel A, Flomenberg N et al. 2011. Evidence for a stromal-epithelial “lactate shuttle” in human tumors. Cell Cycle 10:111772–83
     [Google Scholar]
203. Wilding JL, Bodmer WF. 2014. Cancer cell lines for drug discovery and development. Cancer Res 74:92377–84
     [Google Scholar]
204. Witkiewicz AK, Whitaker-Menezes D, Dasgupta A, Philp NJ, Lin Z et al. 2012. Using the “reverse Warburg effect” to identify high-risk breast cancer patients. Cell Cycle 11:61108–17
     [Google Scholar]
205. Wong BW, Wang X, Zecchin A, Thienpont B, Cornelissen I et al. 2017. The role of fatty acid β-oxidation in lymphangiogenesis. Nature 542:763949–54
     [Google Scholar]
206. Wood GW, Gillespie GY. 1975. Studies on the role of macrophages in regulation of growth and metastasis of murine chemically induced fibrosarcomas. Int. J. Cancer 16:61022–29
     [Google Scholar]
207. Xiao Z, Dai Z, Locasale JW 2019. Metabolic landscape of the tumor microenvironment at single cell resolution. Nat. Commun 103763
208. Xue J, Schmidt SV, Sander J, Draffehn A, Krebs W et al. 2014. Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity 40:2274–88
     [Google Scholar]
209. Yang L, Achreja A, Yeung T-L, Mangala LS, Jiang D et al. 2016. Targeting stromal glutamine synthetase in tumors disrupts tumor microenvironment-regulated cancer cell growth. Cell Metab 24:5685–700
     [Google Scholar]
210. Yao C-H, Liu G-Y, Wang R, Moon SH, Gross RW, Patti GJ 2018. Identifying off-target effects of etomoxir reveals that carnitine palmitoyltransferase I is essential for cancer cell proliferation independent of β-oxidation. PLOS Biol 16:3e2003782
     [Google Scholar]
211. Yeh W-L, Lin C-J, Fu W-M 2008. Enhancement of glucose transporter expression of brain endothelial cells by vascular endothelial growth factor derived from glioma exposed to hypoxia. Mol. Pharmacol. 73:1170–77
     [Google Scholar]
212. Zecchin A, Kalucka J, Dubois C, Carmeliet P 2017. How endothelial cells adapt their metabolism to form vessels in tumors. Front. Immunol. 8:873–78
     [Google Scholar]
213. Zhang Q-W, Liu L, Gong C-Y, Shi H-S, Zeng Y-H et al. 2012. Prognostic significance of tumor-associated macrophages in solid tumor: a meta-analysis of the literature. PLOS ONE 7:12e50946–14
     [Google Scholar]
214. Zhao H, Yang L, Baddour J, Achreja A, Bernard V et al. 2016. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism. eLife 5:e10250
     [Google Scholar]
215. Zhao X, Psarianos P, Ghoraie LS, Yip K, Goldstein D et al. 2019. Metabolic regulation of dermal fibroblasts contributes to skin extracellular matrix homeostasis and fibrosis. Nat. Metab. 1:147–57
     [Google Scholar]