A Mathematical Dissection of the Adaptation of Cell Populations to Fluctuating Oxygen Levels.

A Mathematical Dissection of the Adaptation of Cell Populations to Fluctuating Oxygen Levels. Bull Math Biol. 2020 Jun 16;82(6):81 Authors: Ardaševa A, Gatenby RA, Anderson ARA, Byrne HM, Maini PK, Lorenzi T Abstract The disordered network of blood vessels that arises from tumour angiogenesis results in variations in the delivery of oxygen into the tumour tissue. This brings about regions of chronic hypoxia (i.e. sustained low oxygen levels) and regions with alternating periods of low and relatively higher oxygen levels, and makes it necessary for cancer cells to adapt to fluctuating environmental conditions. We use a phenotype-structured model to dissect the evolutionary dynamics of cell populations exposed to fluctuating oxygen levels. In this model, the phenotypic state of every cell is described by a continuous variable that provides a simple representation of its metabolic phenotype, ranging from fully oxidative to fully glycolytic, and cells are grouped into two competing populations that undergo heritable, spontaneous phenotypic variations at different rates. Model simulations indicate that, depending on the rate at which oxygen is consumed by the cells, dynamic nonlinear interactions between cells and oxygen can stimulate chronic hypoxia and cycling hypoxia. Moreover, the model supports the idea that under chronic-hypoxic conditions lower rates of phenotypic variation lead to a competitive advantage, whereas higher rates of ...
Source: Bulletin of Mathematical Biology - Category: Bioinformatics Authors: Tags: Bull Math Biol Source Type: research