Hypoxia-mediated upregulation of MCT1 expression supports the glycolytic phenotype of glioblastomas

Oncotarget

Volumn 7, Issue 29, 2016, Pages 46335-46353

  Miranda Gonçalves, Vera ^a,b   Granja, Sara ^a,b   Martinho, Olga ^a,b,c   Honavar, Mrinalini ^d   Pojo, Marta ^a,b   Costa, Bruno M ^a,b   Pires, Manuel M ^e   Pinheiro, Célia ^e   Cordeiro, Michelle ^f   Bebiano, Gil ^f   Costa, Paulo ^g   Reis, Rui M ^a,b,c   Baltazar, Fátima ^a,b  

^a UNIVERSITY OF MINHO   (Portugal)

^b UNIVERSITY OF MINHO   (Portugal)

^c BARRETOS CANCER HOSPITAL   (Brazil)

^d HOSPITAL PEDRO HISPANO   (Portugal)

^e Centro Hospitalar Universitario do Porto   (Portugal)

^f Hospital Dr Nélio Mendonça Funchal   (Portugal)

^g Radiotherapy Service   (Portugal)

Author keywords

Glioblastomas; Lactate; Monocarboxylate transporters (MCTs); Tumor hypoxia; Warburg effect

Indexed keywords

ALPHA CYANO 4 HYDROXYCINNAMIC ACID; CELL PROTEIN; GLUCOSE TRANSPORTER 1; LACTIC ACID; MONOCARBOXYLATE TRANSPORTER 1; MONOCARBOXYLATE TRANSPORTER 4; PROTEIN CAIX; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; COTRANSPORTER; MONOCARBOXYLATE TRANSPORT PROTEIN 1; MONOCARBOXYLATE TRANSPORTER;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER TISSUE; CARCINOGENESIS; CELL INVASION; CELL MEMBRANE; CELL METABOLISM; CELL MIGRATION; CELL PROLIFERATION; CELL VIABILITY; CLINICAL ARTICLE; CONTROLLED STUDY; DOWN REGULATION; DRUG TARGETING; GLIOBLASTOMA; GLYCOLYSIS; HUMAN; HUMAN CELL; HUMAN TISSUE; HYPOXIA; IMMUNOFLUORESCENCE TEST; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; IN VIVO STUDY; MALE; MOUSE; NONHUMAN; PHENOTYPE; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; UPREGULATION; WESTERN BLOTTING; ANIMAL; BIOSYNTHESIS; BRAIN TUMOR; CELL HYPOXIA; METABOLISM; NUDE MOUSE; PATHOLOGY; PHYSIOLOGY; TUMOR CELL LINE; XENOGRAFT;

ANIMALS; BRAIN NEOPLASMS; CELL HYPOXIA; CELL LINE, TUMOR; GLIOBLASTOMA; GLYCOLYSIS; HETEROGRAFTS; HUMANS; MICE; MICE, NUDE; MONOCARBOXYLIC ACID TRANSPORTERS; PHENOTYPE; SYMPORTERS; UP-REGULATION;

EID: 84979950555     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.10114     Document Type: Article

References (52)

1. Hanahan D and Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144:646-674.
2. Cairns RA, Harris IS and Mak TW. Regulation of cancer cell metabolism. Nature reviews Cancer. 2011; 11:85-95.
3. Warburg O. On respiratory impairment in cancer cells. Science. 1956; 124:269-270.
4. Gatenby RA and Gillies RJ. Why do cancers have high aerobic glycolysis? Nature reviews Cancer. 2004; 4:891-899.
5. Denko NC. Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nature reviews Cancer. 2008; 8:705-713.
6. Chiche J, Brahimi-Horn MC and Pouyssegur J. Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer. Journal of cellular and molecular medicine. 2010; 14:771-794.
7. Hirschhaeuser F, Sattler UG and Mueller-Klieser W. Lactate: a metabolic key player in cancer. Cancer research. 2011; 71:6921-6925.
8. Riemenschneider MJ and Reifenberger G. Molecular neuropathology of gliomas. International journal of molecular sciences. 2009; 10:184-212.
9. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. The lancet oncology. 2009; 10:459-466.
10. Wolf A, Agnihotri S and Guha A. Targeting metabolic remodeling in glioblastoma multiforme. Oncotarget. 2010; 1:552-562. doi: 10.18632/oncotarget.190.
11. Oudard S, Arvelo F, Miccoli L, Apiou F, Dutrillaux AM, Poisson M, Dutrillaux B and Poupon MF. High glycolysis in gliomas despite low hexokinase transcription and activity correlated to chromosome 10 loss. British journal of cancer. 1996; 74:839-845.
12. Tabatabaei P, Bergstrom P, Henriksson R and Bergenheim AT. Glucose metabolites, glutamate and glycerol in malignant glioma tumours during radiotherapy. Journal of neuro-oncology. 2008; 90:35-39.
13. Izumi H, Torigoe T, Ishiguchi H, Uramoto H, Yoshida Y, Tanabe M, Ise T, Murakami T, Yoshida T, Nomoto M and Kohno K. Cellular pH regulators: potentially promising molecular targets for cancer chemotherapy. Cancer treatment reviews. 2003; 29:541-549.
14. Halestrap AP. The monocarboxylate transporter family-Structure and functional characterization. IUBMB life. 2012; 64:1-9.
15. Halestrap AP and Wilson MC. The monocarboxylate transporter family-role and regulation. IUBMB life. 2012; 64:109-119.
16. Pinheiro C, Longatto-Filho A, Azevedo-Silva J, Casal M, Schmitt FC and Baltazar F. Role of monocarboxylate transporters in human cancers: state of the art. Journal of bioenergetics and biomembranes. 2012; 44:127-139.
17. Miranda-Goncalves V, Honavar M, Pinheiro C, Martinho O, Pires MM, Pinheiro C, Cordeiro M, Bebiano G, Costa P, Palmeirim I, Reis RM and Baltazar F. Monocarboxylate transporters (MCTs) in gliomas: expression and exploitation as therapeutic targets. Neuro-oncology. 2013; 15:172-188.
18. Halestrap AP. Monocarboxylic acid transport. Comprehensive Physiology. 2013; 3:1611-1643.
19. Kim JW, Gao P and Dang CV. Effects of hypoxia on tumor metabolism. Cancer metastasis reviews. 2007; 26:291-298.
20. Ord JJ, Streeter EH, Roberts IS, Cranston D and Harris AL. Comparison of hypoxia transcriptome in vitro with in vivo gene expression in human bladder cancer. Br J Cancer. 2005; 93:346-354.
21. Sonveaux P, Vegran F, Schroeder T, Wergin MC, Verrax J, Rabbani ZN, De Saedeleer CJ, Kennedy KM, Diepart C, Jordan BF, Kelley MJ, Gallez B, Wahl ML, Feron O and Dewhirst MW. Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J Clin Invest. 2008; 118:3930-3942.
22. Cheng C, Edin NF, Lauritzen KH, Aspmodal I, Christoffersen S, Jian L, Rasmussen LJ, Pettersen EO, Xiaoqun G and Bergersen LH. Alterations of monocarboxylate transporter densities during hypoxia in brain and breast tumour cells. Cell Oncol (Dordr). 2012; 35:217-227.
23. Doyen J, Trastour C, Ettore F, Peyrottes I, Toussant N, Gal J, Ilc K, Roux D, Parks SK, Ferrero JM and Pouyssegur J. Expression of the hypoxia-inducible monocarboxylate transporter MCT4 is increased in triple negative breast cancer and correlates independently with clinical outcome. Biochemical and biophysical research communications. 2014; 451:54-61.
24. McClelland GB and Brooks GA. Changes in MCT 1, MCT 4, and LDH expression are tissue specific in rats after longterm hypobaric hypoxia. Journal of applied physiology. 2002; 92:1573-1584.
25. Kay HH, Zhu S and Tsoi S. Hypoxia and lactate production in trophoblast cells. Placenta. 2007; 28:854-860.
26. Perez de Heredia F, Wood IS and Trayhurn P. Hypoxia stimulates lactate release and modulates monocarboxylate transporter (MCT1, MCT2, and MCT4) expression in human adipocytes. Pflugers Archiv: European journal of physiology. 2010; 459:509-518.
27. Ullah MS, Davies AJ and Halestrap AP. The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by hypoxia through a HIF-1alpha-dependent mechanism. J Biol Chem. 2006; 281:9030-9037.
28. Zhang F, Vannucci SJ, Philp NJ and Simpson IA. Monocarboxylate transporter expression in the spontaneous hypertensive rat: effect of stroke. J Neurosci Res. 2005; 79:139-145.
29. Linnik IV, Scott ML, Holliday KF, Woodhouse N, Waterton JC, O'Connor JP, Barjat H, Liess C, Ulloa J, Young H, Dive C, Hodgkinson CL, Ward T, Roberts D, Mills SJ, Thompson G, et al. Noninvasive tumor hypoxia measurement using magnetic resonance imaging in murine U87 glioma xenografts and in patients with glioblastoma. Magnetic resonance in medicine. 2014; 71:1854-1862.
30. Jensen RL. Brain tumor hypoxia: tumorigenesis, angiogenesis, imaging, pseudoprogression, and as a therapeutic target. Journal of neuro-oncology. 2009; 92:317-335.
31. Yang L, Lin C, Wang L, Guo H and Wang X. Hypoxia and hypoxia-inducible factors in glioblastoma multiforme progression and therapeutic implications. Experimental cell research. 2012; 318:2417-2426.
32. Boidot R, Vegran F, Meulle A, Le Breton A, Dessy C, Sonveaux P, Lizard-Nacol S and Feron O. Regulation of monocarboxylate transporter MCT1 expression by p53 mediates inward and outward lactate fluxes in tumors. Cancer research. 2012; 72:939-948.
33. Halestrap AP and Meredith D. The SLC16 gene familyfrom monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Archiv: European journal of physiology. 2004; 447:619-628.
34. Halestrap AP. Transport of pyruvate nad lactate into human erythrocytes. Evidence for the involvement of the chloride carrier and a chloride-independent carrier. The Biochemical journal. 1976; 156:193-207.
35. Marchiq I, Le Floch R, Roux D, Simon MP and Pouyssegur J. Genetic disruption of lactate/H+ symporters (MCTs) and their subunit CD147/BASIGIN sensitizes glycolytic tumor cells to phenformin. Cancer research. 2015; 75:171-180.
36. Morais-Santos F, Miranda-Goncalves V, Pinheiro S, Vieira AF, Paredes J, Schmitt FC, Baltazar F and Pinheiro C. Differential sensitivities to lactate transport inhibitors of breast cancer cell lines. Endocrine-related cancer. 2014; 21:27-38.
37. Brandsma D and van den Bent MJ. Molecular targeted therapies and chemotherapy in malignant gliomas. Current opinion in oncology. 2007; 19:598-605.
38. Colen CB, Shen Y, Ghoddoussi F, Yu P, Francis TB, Koch BJ, Monterey MD, Galloway MP, Sloan AE and Mathupala SP. Metabolic targeting of lactate efflux by malignant glioma inhibits invasiveness and induces necrosis: an in vivo study. Neoplasia. 2011; 13:620-632.
39. Gallagher SM, Castorino JJ and Philp NJ. Interaction of monocarboxylate transporter 4 with beta1-integrin and its role in cell migration. American journal of physiology Cell physiology. 2009; 296:C414-421.
40. Fujiwara S, Nakagawa K, Harada H, Nagato S, Furukawa K, Teraoka M, Seno T, Oka K, Iwata S and Ohnishi T. Silencing hypoxia-inducible factor-1alpha inhibits cell migration and invasion under hypoxic environment in malignant gliomas. International journal of oncology. 2007; 30:793-802.
41. Coady MJ, Chang MH, Charron FM, Plata C, Wallendorff B, Sah JF, Markowitz SD, Romero MF and Lapointe JY. The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter. The Journal of physiology. 2004; 557:719-731.
42. Grillon E, Farion R, Fablet K, De Waard M, Tse CM, Donowitz M, Remy C and Coles JA. The spatial organization of proton and lactate transport in a rat brain tumor. PloS one. 2011; 6:e17416.
43. Rademakers SE, Lok J, van der Kogel AJ, Bussink J and Kaanders JH. Metabolic markers in relation to hypoxia; staining patterns and colocalization of pimonidazole, HIF-1alpha, CAIX, LDH-5, GLUT-1, MCT1 and MCT4. BMC cancer. 2011; 11:167.
44. Oliver L, Olivier C, Marhuenda FB, Campone M and Vallette FM. Hypoxia and the malignant glioma microenvironment: regulation and implications for therapy. Current molecular pharmacology. 2009; 2:263-284.
45. Flynn JR, Wang L, Gillespie DL, Stoddard GJ, Reid JK, Owens J, Ellsworth GB, Salzman KL, Kinney AY and Jensen RL. Hypoxia-regulated protein expression, patient characteristics, and preoperative imaging as predictors of survival in adults with glioblastoma multiforme. Cancer. 2008; 113:1032-1042.
46. Proescholdt MA, Merrill MJ, Stoerr EM, Lohmeier A, Pohl F and Brawanski A. Function of carbonic anhydrase IX in glioblastoma multiforme. Neuro-oncology. 2012; 14:1357-1366.
47. Pinheiro C, Sousa B, Albergaria A, Paredes J, Dufloth R, Vieira D, Schmitt F and Baltazar F. GLUT1 and CAIX expression profiles in breast cancer correlate with adverse prognostic factors and MCT1 overexpression. Histology and histopathology. 2011; 26:1279-1286.
48. Meijer TW, Schuurbiers OC, Kaanders JH, Looijen-Salamon MG, de Geus-Oei LF, Verhagen AF, Lok J, van der Heijden HF, Rademakers SE, Span PN and Bussink J. Differences in metabolism between adeno-and squamous cell non-small cell lung carcinomas: spatial distribution and prognostic value of GLUT1 and MCT4. Lung cancer. 2012; 76:316-323.
49. Morais-Santos F, Granja S, Miranda-Goncalves V, Moreira AH, Queiros S, Vilaca JL, Schmitt FC, Longatto-Filho A, Paredes J, Baltazar F and Pinheiro C. Targeting lactate transport suppresses in vivo breast tumour growth. Oncotarget. 2015; 6:19177-19189. doi: 10.18632/oncotarget.3910.
50. Moniz S, Martinho O, Pinto F, Sousa B, Loureiro C, Oliveira MJ, Moita LF, Honavar M, Pinheiro C, Pires M, Lopes JM, Jones C, Costello JF, Paredes J, Reis RM and Jordan P. Loss of WNK2 expression by promoter gene methylation occurs in adult gliomas and triggers Rac1-mediated tumour cell invasiveness. Human molecular genetics. 2013; 22:84-95.
51. Martinho O, Pinto F, Granja S, Miranda-Goncalves V, Moreira MA, Ribeiro LF, di Loreto C, Rosner MR, Longatto-Filho A and Reis RM. RKIP inhibition in cervical cancer is associated with higher tumor aggressive behavior and resistance to cisplatin therapy. PloS one. 2013; 8:e59104.
52. Pojo M, Goncalves CS, Xavier-Magalhaes A, Oliveira AI, Goncalves T, Correia S, Rodrigues AJ, Costa S, Pinto L, Pinto AA, Lopes JM, Reis RM, Rocha M, Sousa N and Costa BM. A transcriptomic signature mediated by HOXA9 promotes human glioblastoma initiation, aggressiveness and resistance to temozolomide. Oncotarget. 2015; 6:7657-7674 doi: 10.18632/oncotarget.3150.