Heterogeneity and proliferation of invasive cancer subclones in game theory models of the Warburg effect

Archetti, Marco (2015) Heterogeneity and proliferation of invasive cancer subclones in game theory models of the Warburg effect. Cell Proliferation, 48 (2). 259–269. ISSN 1365-2184

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Abstract

OBJECTIVES: The Warburg effect, the switch from aerobic energy production to anaerobic glycolysis, promotes tumour proliferation and motility by inducing acidification of the tumour microenvironment. Therapies that reduce acidity could impair tumour growth and invasiveness. I analyse the dynamics of cell proliferation and of resistance to therapies that target acidity in a population of cells under the Warburg effect. MATERIALS AND METHODS: The dynamics of mutant cells with increased glycolysis and motility is analysed in a multi-player game with collective interactions in the framework of evolutionary game theory. Perturbations of the level of acidity in the microenvironment are used to simulate the effect of therapies that target glycolysis. RESULTS: The non-linear effects of glycolysis induce frequency-dependent clonal selection leading to the coexistence of glycolytic and non-glycolytic cells within the tumour. Mutants with increased motility can invade such polymorphic population and spread within the tumour. While reducing acidity may produce a sudden reduction in tumour proliferation, frequency-dependent selection enables the tumour to adapt to the new conditions and can enable the tumour to restore the original levels of growth and invasiveness. CONCLUSIONS: The acidity produced by glycolysis acts as a non-linear public good that leads to the coexistence of cells with high and low glycolysis within the tumour. Such heterogeneous population can easily adapt to changes in acidity. Therapies that target acidity can only be effective in the long term if the cost of glycolysis is high, that is, under non-limiting oxygen concentrations. Their efficacy, therefore, is reduced when combined with therapies that impair angiogenesis.

Item Type: Article
Additional Information: © 2015 The Authors Cell Proliferation Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Pure Connector
Date Deposited: 02 Feb 2015 13:48
Last Modified: 18 Nov 2020 00:36
URI: https://ueaeprints.uea.ac.uk/id/eprint/52013
DOI: 10.1111/cpr.12169

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