Case Studies in Modelling Collective Cell Motion in Biology
Philip K MainiWolfson Centre for Mathematical Biology
Mathematical InstOxford
UK
Acid-Mediated Invasion Hypothesis
• A bi-product of the glycolytic pathway is lactic acid – this lowers the extracellular pH so that it favours tumour cell proliferation AND it is toxic to normal cells.
• R.A. Gatenby and E.T. Gawslinski, A reaction-diffusion model of cancer invasion, Cancer Research, 56, 5745-5753 (1996)
The alphas
• GLUT expression is hypoxia-induced, MCT1 expression is hypoxia-repressed.
• If cell expression of MCT1 is high relative to that for GLUT, then alpha_L > alpha_G etc
Results
• Symbiosis is possible but requires metabolic activity several orders of magnitude higher than observed in vitro.
Conclusions
• Explored effects of metabolism in tumour growth.
• Used a multiscale model of the crypt to explore the effects of key processes thought to determine cell progression and fixing.