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A partial differential equation model is developed to understand the effect that nutrient and acidosis have on the distribution of proliferating and quiescent cells and dead cell material (necrotic and apoptotic) within a multicellular tumour spheroid. The rates of cell quiescence and necrosis depend upon the local nutrient and acid concentrations and quiescent cells are assumed to consume less nutrient and produce less acid than proliferating cells. Analysis of the differences in nutrient consumption and acid production by quiescent and proliferating cells shows low nutrient levels do not necessarily lead to increased acid concentration via anaerobic metabolism. Rather, it is the balance between proliferating and quiescent cells within the tumour which is important; decreased nutrient levels lead to more quiescent cells, which produce less acid than proliferating cells. We examine this effect via a sensitivity analysis which also includes a quantification of the effect that nutrient and acid concentrations have on the rates of cell quiescence and necrosis.

Original publication

DOI

10.1016/j.jtbi.2011.11.009

Type

Journal article

Journal

J Theor Biol

Publication Date

07/04/2012

Volume

298

Pages

107 - 115

Keywords

Acidosis, Apoptosis, Cell Cycle, Cell Death, Cell Proliferation, Humans, Models, Biological, Necrosis, Neoplasms, Spheroids, Cellular, Tumor Cells, Cultured