A2
Multi-scale modelling of oxygen, glucose, lactic acid and pH gradients in tumours
Christopher Catt, Colin Please, Tina Roose
University of Southampton, UK
An essential task in tumour biology is to understand the microenvironment of tumour cells. A tumour is a cellular region experiencing uncontrolled cell proliferation. This produces a region of densely packed cells consuming large quantities of nutrients and producing equally as much waste. The efficiency of radiotherapy and chemotherapy are sensitive to the local environment [1]. We will investigate the changes to the microenvironment of a tumour using mathematical modelling tools in combination with experimental data.
Mathematical modelling of tumour growth has been focused most commonly on growth due to the concentration of a generic nutrient, usually oxygen [2]. We will look in detail at the metabolic pathways from which cells obtain energy (ATP) and model the distribution of oxygen, glucose, lactic acid and pH within avascular regions of tumours.
Building on work by Casciari et al [3], we consider a growing tumour and the transition of ATP production from aerobic respiration through to anaerobic respiration. The relevant buffering reactions are included together with waste production by cells (carbon dioxide, lactic acid and pH). In addition to the diffusive effects on nutrient movement we include the effects of charge migration on ionic molecules.
The ideas and structure of the model are applied to modelling avascular multi cellular tumour spheroids (MCTS). The MCTS is shown to expand at a rate determined by its potential ATP production balanced by inhibition due to the concentration of waste. The model also shows characteristics of a cells functional state being determined by its location and local environment, with regions of proliferation, quiescence and necrosis appearing naturally. We will briefly discuss the implications of our findings to tumour imaging and treatment.
References
[1] Tredan, O., Galmarini C.M., Patel, K., Tannock I.F. (2007) J Natl Cancer Inst. 99: 1441-1454
[2] Roose, T., Chapman, S.J., Maini, P.K. (2007) Siam Review. 49: 179-208
[3] Casciari, J. J., Sotirchos, S.V., and Sutherland, R. M. (1992) Cell Prolif. 25:1-22
