Abstract
The aim of the study was to assess the link between the metabolic profile and the proliferation capacity of a range of human and murine cancer cell lines. First, the combination of mitochondrial respiration and glycolytic efficiency measurements allowed the determination of different metabolic profiles among the cell lines, ranging from a mostly oxidative to a mostly glycolytic phenotype. Second, the study revealed that cell proliferation, evaluated by DNA synthesis measurements, was statistically correlated to glycolytic efficiency. This indicated that glycolysis is the key energetic pathway linked to cell proliferation rate. Third, to validate this hypothesis and exclude non-metabolic factors, mitochondria-depleted were compared to wild-type cancer cells, and the data showed that enhanced glycolysis observed in mitochondria-depleted cells is also associated with an increase in proliferation capacity.
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References
Warburg O (1925) Uber den Stoffwechsel der Carcinomzelle. Klin Wochenschr 4:534–536
Penta JS, Johnson FM, Wachsman JT et al (2001) Mitochondrial DNA in human malignancy. Mutat Res 488:119–133
Xu RH, Pelicano H, Zhou Y et al (2005) Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia. Cancer Res 65:613–621
Moreno-Sanchez R, Marin-Hernandez A, Saavedra E, Pardo JP et al (2014) Who controls the ATP supply in cancer cells? Biochemistry lessons to understand cancer energy metabolism. Int J Biochem Cell Biol 50:10–23
Moreno-Sanchez R, Rodriguez-Enriquez S, Marin-Hernandez A et al (2007) Energy metabolism in tumor cells. FEBS J 274:1393–1418
Zu XL, Guppy M (2004) Cancer metabolism: facts, fantasy, and fiction. Biochem Biophys Res Commun 313:459–465
Diepart C, Verrax J, Calderon PB et al (2010) Comparison of methods for measuring oxygen consumption in tumor cells in vitro. Anal Biochem 396:250–256
Taper HS, Woolley GW, Teller MN et al (1966) A new transplantable mouse liver tumor of spontaneous origin. Cancer Res 26:143–148
Volpe JP, Hunter N, Basic I et al (1985) Metastatic properties of murine sarcomas and carcinomas. I. Positive correlation with lung colonization and lack of correlation with s.c. tumor take. Clin Exp Metastasis 3:281–294
Rockwell S, Kallman RF (1972) Growth and cell population kinetics of single and multiple KHT sarcomas. Cell Tissue Kinet 5:449–457
Reilly RT, Gottlieb MB, Ercolini AM et al (2000) HER-2/neu is a tumor rejection target in tolerized HER-2/neu transgenic mice. Cancer Res 60:3569–3576
King MP, Attardi G (1989) Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation. Science 246:500–503
James PE, Jackson SK, Grinberg OY et al (1995) The effects of endotoxin on oxygen consumption of various cell types in vitro: an EPR oximetry study. Free Radic Biol Med 18:641–647
Jordan BF, Gregoire V, Demeure RJ et al (2002) Insulin increases the sensitivity of tumors to irradiation: involvement of an increase in tumor oxygenation mediated by a nitric oxide-dependent decrease of the tumor cells oxygen consumption. Cancer Res 62:3555–3561
Fogal V, Richardson AD, Karmali PP et al (2010) Mitochondrial p32 protein is a critical regulator of tumor metabolism via maintenance of oxidative phosphorylation. Mol Cell Biol 30:1303–1318
Lunt SY, Vander Heiden MG (2011) Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol 27:441–464
Hume DA, Weidemann MJ (1979) Role and regulation of glucose metabolism in proliferating cells. J Natl Cancer Inst 62:3–8
Hedeskov CJ (1968) Early effects of phytohaemagglutinin on glucose metabolism of normal human lymphocytes. Biochem J 110:373–380
Tannock IF (1968) The relation between cell proliferation and the vascular system in a transplanted mouse mammary tumour. Br J Cancer 22:258–273
Acknowledgments
This work was supported by grants from the Télévie, the Belgian National Fund for Scientific Research (F.R.S.-FNRS), the Fonds Joseph Maisin, the Fondation Belge contre le Cancer, the Saint-Luc Foundation, the Actions de Recherches Concertées-Communauté Française de Belgique (ARC 04/09-317), and the European Research Council (FP7/2007-2013 ERC Independent Researcher Starting Grant No. 243188 TUMETABO). B.F.J. and P.S. are Research Associates and P.D. a Research Fellow of the F.R.S.-FNRS. G.D. is a Télévie Research Fellow.
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De Preter, G. et al. (2016). Direct Evidence of the Link Between Energetic Metabolism and Proliferation Capacity of Cancer Cells In Vitro. In: Elwell, C.E., Leung, T.S., Harrison, D.K. (eds) Oxygen Transport to Tissue XXXVII. Advances in Experimental Medicine and Biology, vol 876. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3023-4_26
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DOI: https://doi.org/10.1007/978-1-4939-3023-4_26
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