Format

Send to

Choose Destination
See comment in PubMed Commons below
Biotechnol J. 2013 Sep;8(9):1058-69. doi: 10.1002/biot.201200393. Epub 2013 Jun 26.

Metabolic gradients as key regulators in zonation of tumor energy metabolism: a tissue-scale model-based study.

Author information

1
Institute of Biochemistry, University Medicine Charité Berlin, Berlin, Germany. matthias.koenig@charite.de.

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 in promotion of 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 center 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 that metabolite availability functions as key regulator of tumor energy metabolism.

KEYWORDS:

Hypoxia; Metabolic reprogramming; Metabolic zonation; Oxygen; Warburg effect

PMID:
23589477
DOI:
10.1002/biot.201200393
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Support Center