The Mathematical Institute, University of Oxford, Eprints Archive

Episodic, transient systemic acidosis delays evolution of the malignant phenotype: Possible mechanism for cancer prevention by increased physical activity

Smallbone, K. and Maini, P. K. and Gatenby, R. A. (2010) Episodic, transient systemic acidosis delays evolution of the malignant phenotype: Possible mechanism for cancer prevention by increased physical activity. Biology Direct, 5 (22). pp. 1-8.

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Abstract

Background

The transition from premalignant to invasive tumour growth is a prolonged multistep process governed by phenotypic adaptation to changing microenvironmental selection pressures. Cancer prevention strategies are required to interrupt or delay somatic evolution of the malignant invasive phenotype. Empirical studies have consistently demonstrated that increased physical activity is highly effective in reducing the risk of breast cancer but the mechanism is unknown.

Results

Here we propose the hypothesis that exercise-induced transient systemic acidosis will alter the in situ tumour microenvironment and delay tumour adaptation to regional hypoxia and acidosis in the later stages of carcinogenesis. We test this hypothesis using a hybrid cellular automaton approach. This model has been previously applied to somatic evolution on epithelial surfaces and demonstrated three phases of somatic evolution, with cancer cells escaping in turn from the constraints of limited space, nutrient supply and waste removal. In this paper we extend the model to test our hypothesis that transient systemic acidosis is sufficient to arrest, or at least delay, transition from in situ to invasive cancer.

Conclusions

Model simulations demonstrate that repeated episodes of transient systemic acidosis will interrupt critical evolutionary steps in the later stages of carcinogenesis resulting in substantial delay in the evolution to the invasive phenotype. Our results suggest transient systemic acidosis may mediate the observed reduction in cancer risk associated with increased physical activity.

Item Type:Article
Subjects:A - C > Biology and other natural sciences
Research Groups:Centre for Mathematical Biology
ID Code:919
Deposited By:Philip Maini
Deposited On:07 May 2010 08:38
Last Modified:08 Oct 2012 14:35

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