Cancer-generated lactic acid: A regulatory, immunosuppressive metabolite?

Journal of Pathology

Volumn 230, Issue 4, 2013, Pages 350-355

  Choi, Stephen Yiu Chuen ^a   Collins, Colin C ^b,c   Gout, Peter W ^a   Wang, Yuzhuo ^a  

^a BRITISH COLUMBIA CANCER AGENCY   (Canada)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^c VANCOUVER PROSTATE CENTRE   (Canada)

Author keywords

aerobic glycolysis; glutaminolysis; immune suppression; lactic acid; tumour micro environment; Warburg effect

Indexed keywords

ADENOSINE TRIPHOSPHATE; ANTINEOPLASTIC AGENT; ASPARTIC ACID; DNA; GLUCOSE; GLUTAMIC ACID; GLUTAMINE; IMMUNOMODULATING AGENT; LACTIC ACID; MYC PROTEIN; OXYGEN; PROTEIN KINASE B; RAS PROTEIN; REACTIVE OXYGEN METABOLITE;

ACIDIFICATION; AEROBIC METABOLISM; AUTOPHAGY; CANCER CELL; CANCER CHEMOTHERAPY; CANCER GROWTH; CANCER IMMUNOTHERAPY; CANCER RADIOTHERAPY; CANCER THERAPY; CARCINOGENESIS; CELL HYPOXIA; CELL MATURATION; CELL PROLIFERATION; CELL SURFACE; CELL TRANSFORMATION; CITRIC ACID CYCLE; DNA DAMAGE; ENERGY METABOLISM; EPITHELIAL IMMUNE CELL LIKE TRANSITION; GLUCOSE TRANSPORT; HELPER CELL; HUMAN; IMMUNE RESPONSE; IMMUNOMODULATION; LACTATE BLOOD LEVEL; METABOLITE; NEOPLASM; NEUROBLASTOMA CELL; OXIDATIVE PHOSPHORYLATION; PH; PRIORITY JOURNAL; PROTEIN SYNTHESIS; REVIEW; TUMOR MICROENVIRONMENT;

AEROBIC GLYCOLYSIS; GLUTAMINOLYSIS; IMMUNE SUPPRESSION; LACTIC ACID; TUMOUR MICRO-ENVIRONMENT; WARBURG EFFECT;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL SURVIVAL; DRUG DESIGN; ENERGY METABOLISM; GLYCOLYSIS; HUMANS; HYDROGEN-ION CONCENTRATION; LACTIC ACID; MOLECULAR TARGETED THERAPY; NEOPLASMS; SIGNAL TRANSDUCTION; TUMOR ESCAPE; TUMOR MICROENVIRONMENT;

EID: 84880120014     PISSN: 00223417     EISSN: 10969896     Source Type: Journal    
DOI: 10.1002/path.4218     Document Type: Review

References (53)

1. Warburg O., On respiratory impairment in cancer cells. Science 1956; 124: 269-270.
2. Feron O., Pyruvate into lactate and back: from the Warburg effect to symbiotic energy fuel exchange in cancer cells. Radiother Oncol 2009; 92: 329-333.
3. Hsu PP, Sabatini DM,. Cancer cell metabolism: Warburg and beyond. Cell 2008; 134: 703-707.
4. Shaw RJ,. Glucose metabolism and cancer. Curr Opin Cell Biol 2006; 18: 598-608.
5. Jadvar H, Alavi A, Gambhir SS,. 18F-FDG uptake in lung, breast, and colon cancers: molecular biology correlates and disease characterization. J Nucl Med 2009; 50: 1820-1827.
6. DeBerardinis RJ, Cheng T,. Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene 2010; 29: 313-324.
7. Deberardinis RJ, Sayed N, Ditsworth D, et al,. Brick by brick: metabolism and tumor cell growth. Curr Opin Genet Dev 2008; 18: 54-61.
8. Hanahan D, Weinberg RA,. Hallmarks of cancer: the next generation. Cell 2011; 144: 646-674.
9. Daye D, Wellen KE,. Metabolic reprogramming in cancer: unraveling the role of glutamine in tumorigenesis. Semin Cell Dev Biol 2012; 23: 362-369.
10. Webb BA, Chimenti M, Jacobson MP, et al,. Dysregulated pH: a perfect storm for cancer progression. Nature Rev Cancer 2011; 11: 671-677.
11. Calcinotto A, Filipazzi P, Grioni M, et al,. Modulation of microenvironment acidity reverses anergy in human and murine tumor-infiltrating T lymphocytes. Cancer Res 2012; 72: 2746-2756.
12. De Milito A, Canese R, Marino ML, et al,. pH-dependent antitumor activity of proton pump inhibitors against human melanoma is mediated by inhibition of tumor acidity. Int J Cancer 2010; 127: 207-219.
13. Gatenby RA, Gillies RJ,. Why do cancers have high aerobic glycolysis? Nature Rev Cancer 2004; 4: 891-899.
14. Warburg O., On the origin of cancer cells. Science 1956; 123: 309-314.
15. Chandra D, Singh KK,. Genetic insights into OXPHOS defect and its role in cancer. Biochim Biophys Acta 2011; 1807: 620-625.
16. Fantin VR, St-Pierre J, Leder P,. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell 2006; 9: 425-434.
17. Kimura H, Braun RD, Ong ET, et al,. Fluctuations in red cell flux in tumor microvessels can lead to transient hypoxia and reoxygenation in tumor parenchyma. Cancer Res 1996; 56: 5522-5528.
18. Draoui N, Feron O,. Lactate shuttles at a glance: from physiological paradigms to anti-cancer treatments. Dis Model Mech 2011; 4: 727-732.
19. Vander Heiden MG, Cantley LC, Thompson CB,. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009; 324: 1029-1033.
20. Zu XL, Guppy M,. Cancer metabolism: facts, fantasy, and fiction. Biochem Biophys Res Commun 2004; 313: 459-465.
21. Harjes U, Bensaad K, Harris AL,. Endothelial cell metabolism and implications for cancer therapy. Br J Cancer 2012; 107: 1207-1212.
22. 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 2013; 273: 156-165.
23. Hamaï A, Benlalam H, Meslin F, et al,. Immune surveillance of human cancer: if the cytotoxic T-lymphocytes play the music, does the tumoral system call the tune? Tissue Antigens 2010; 75: 1-8.
24. Lardner A., The effects of extracellular pH on immune function. J Leukoc Biol 2001; 69: 522-530.
25. Kellum JA,. Metabolic acidosis in patients with sepsis: epiphenomenon or part of the pathophysiology? Crit Care Resusc 2004; 6: 197-203.
26. Kellum JA, Song M, Li J,. Lactic and hydrochloric acids induce different patterns of inflammatory response in LPS-stimulated RAW 264.7 cells. Am J Physiol Regul Integr Comp Physiol 2004; 286: R686-R692.
27. Gottfried E, Kunz-Schughart LA, Ebner S, et al,. Tumor-derived lactic acid modulates dendritic cell activation and antigen expression. Blood 2006; 107: 2013-2021.
28. Fischer K, Hoffmann P, Voelkl S, et al,. Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood 2007; 109: 3812-3819.
29. Goetze K, Walenta S, Ksiazkiewicz M, et al,. Lactate enhances motility of tumor cells and inhibits monocyte migration and cytokine release. Int J Oncol 2011; 39: 453-463.
30. Mendler AN, Hu B, Prinz PU, et al,. Tumor lactic acidosis suppresses CTL function by inhibition of p38 and JNK/c-Jun activation. Int J Cancer 2012; 131: 633-640.
31. Ohashi T, Akazawa T, Aoki M, et al,. Dichloroacetate improves immune dysfunction caused by tumor-secreted lactic acid and increases antitumor immunoreactivity. Int J Cancer 2013; DOI: 10.1002/ijc.28114.
32. Mazzio EA, Boukli N, Rivera N, et al,. Pericellular pH homeostasis is a primary function of the Warburg effect: inversion of metabolic systems to control lactate steady state in tumor cells. Cancer Sci 2012; 103: 422-432.
33. Sola-Penna M., Metabolic regulation by lactate. IUBMB Life 2008; 60: 605-608.
34. Hirschhaeuser F, Sattler UG, Mueller-Klieser W,. Lactate: a metabolic key player in cancer. Cancer Res 2011; 71: 6921-6925.
35. Yao F, Zhao T, Zhong C, et al,. LDHA is necessary for the tumorigenicity of esophageal squamous cell carcinoma. Tumour Biol 2013; 34: 25-31.
36. Zhang Y, Zhang X, Wang X, et al,. Inhibition of LDH-A by lentivirus-mediated small interfering RNA suppresses intestinal-type gastric cancer tumorigenicity through the downregulation of Oct4. Cancer Lett 2012; 321: 45-54.
37. Gallagher SM, Castorino JJ, Wang D, et al,. Monocarboxylate transporter 4 regulates maturation and trafficking of CD147 to the plasma membrane in the metastatic breast cancer cell line MDA-MB-231. Cancer Res 2007; 67: 4182-4189.
38. Pértega-Gomes N, Vizcaíno JR, Miranda-Gonçalves V, et al,. Monocarboxylate transporter 4 (MCT4) and CD147 overexpression is associated with poor prognosis in prostate cancer. BMC Cancer 2011; 11: 312.
39. Choi SY, Gout PW, Collins CC, et al,. Epithelial immune cell-like transition (EIT): a proposed transdifferentiation process underlying immune-suppressive activity of epithelial cancers. Differentiation 2012; 83: 293-298.
40. Sena LA, Chandel NS,. Physiological roles of mitochondrial reactive oxygen species. Mol Cell 2012; 48: 158-167.
41. Scatena R, Bottoni P, Pontoglio A, et al,. Glycolytic enzyme inhibitors in cancer treatment. Expert Opin Investig Drugs 2008; 17: 1533-1545.
42. Matsumoto S, Batra S, Saito K, et al,. Antiangiogenic agent sunitinib transiently increases tumor oxygenation and suppresses cycling hypoxia. Cancer Res 2011; 71: 6350-6359.
43. Goel S, Duda DG, Xu L, et al,. Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev 2011; 91: 1071-1121.
44. Izumi H, Torigoe T, Ishiguchi H, et al,. Cellular pH regulators: potentially promising molecular targets for cancer chemotherapy. Cancer Treat Rev 2003; 29: 541-549.
45. Robey IF, Baggett BK, Kirkpatrick ND, et al,. Bicarbonate increases tumor pH and inhibits spontaneous metastases. Cancer Res 2009; 69: 2260-2268.
46. McBrian MA, Behbahan IS, Ferrari R, et al,. Histone acetylation regulates intracellular pH. Mol Cell 2013; 49: 310-321.
47. Buijs M, Vossen JA, Geschwind JF, et al,. Specificity of the anti-glycolytic activity of 3-bromopyruvate confirmed by FDG uptake in a rat model of breast cancer. Invest New Drugs 2009; 27: 120-123.
48. Kim HS, Masko EM, Poulton SL, et al,. Carbohydrate restriction and lactate transporter inhibition in a mouse xenograft model of human prostate cancer. BJU Int 2012; 110: 1062-1069.
49. Anastasiou D, Yu Y, Israelsen WJ, et al,. Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nature Chem Biol 2012; 8: 839-847.
50. Pelicano H, Martin DS, Xu RH, et al,. Glycolysis inhibition for anticancer treatment. Oncogene 2006; 25: 4633-4646.
51. Guais A, Baronzio G, Sanders E, et al,. Adding a combination of hydroxycitrate and lipoic acid (METABLOC™) to chemotherapy improves effectiveness against tumor development: experimental results and case report. Invest New Drugs 2012; 30: 200-211.
52. Singer K, Gottfried E, Kreutz M, et al,. Suppression of T-cell responses by tumor metabolites. Cancer Immunol Immunother 2011; 60: 425-431.
53. Villalba M, Rathore MG, Lopez-Royuela N, et al,. From tumor cell metabolism to tumor immune escape. Int J Biochem Cell Biol 2013; 45: 106-113.