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Metabolic Gradients as Key Regulators in Zonation of Tumor Energy Metabolism: A Tissue-scale Model Based Study

Abstract:

Characteristics of many tumor types are the reprogramming of metabolism and the occurrence of regional hypoxia. In this work we investigated the hypothesis that metabolic reprogramming in combination with metabolic zonation of cellular energy metabolism are important factors to promote the growth capacity of solid tumors. A tissue-scale model of the two main ATP delivering pathways, glycolysis (GLY) and oxidative phosphorylation (OXP) was used to simulate the energy metabolism within solid tumors under various metabolic strategies. Remarkably, despite the high diversity in the usage of glucose, lactate and oxygen in various spatial regions, the tumor as a whole clearly displays the hallmark of the so-called Warburg effect, i.e. a high rate of glucose consumption and lactate production in the presence of sufficiently high levels of oxygen. Our simulations suggest that an increase in GLY capacity and concomitant decrease in OXP capacity from the periphery towards the centre of the tumor improves the availability of oxygen to pericentral tumor cells. The found relationship between the regional oxygen level and the relative share of GLY and OXP capacities supports the view of metabolite availability to function as key regulators of tumor energy metabolism.

23589477

Projects: C3: Zonation of metabolism and its regulation

Biotechnol J
Biotechnol J 8(9): 1058-69
17th Apr 2013

Matthias König, Hermann-Georg Holzhütter, Nikolaus Berndt

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[Matthias König] [Hermann-Georg Holzhütter] [Nikolaus Berndt]

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Views: 1706
  • Created: 6th May 2013 at 09:31
  • Last updated: 24th Oct 2013 at 16:14

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