Metabolic symbiosis between oxygenated and hypoxic tumour cells: An agent-based modelling study
Fig 3
(A). If MCT1 is not mutated (MCT1wt), symbiosis is observed, while when MCT1 is mutated with loss of function (MCT1-), symbiosis is not observed. Different cell populations are shown: OXPHOS (blue cells, glucose/lactate—> pyruvate—>OXPHOS), Glycolysis (green cells, glucose—>pyruvate—>lactate), both OXPHOS and glycolysis (purple cells), not metabolically active or quiescence (gray cells). Gradients of glucose, lactate, tumour growth factor alpha (TGFA) and pH are shown on the microenvironment. (B, C). Number of total, glycoATP and mitoATP cells are shown. The total number of cells contains all the cells in the tumour including dead cells. The mitoATP and glycoATP are the number of cells that rely on OXPHOS and glycolysis for ATP production, respectively. (D, E). Number of hypoxic and oxygenated tumour cells with MCT1 wild type and mutated condition are shown. The hypoxic cell population is not seen when symbiosis is lost (MCT1-) because oxygen cannot be depleted fast enough without lactate oxidation. (F, G). Metabolic symbiosis index and number of active (viable) cells are shown when tumour grows with MCT1wt and MCT1-, so with and without symbiosis. The metabolic symbiosis index quantifies the strength of symbiosis between hypoxic and oxygenated tumour cells. The index can range from 0 to 1 depending on the symbiosis strength. The active cells are the cells with their metabolic pathways are active (i.e., blue, green and purple cells shown in A). The shaded area of curves shows respective standard deviation.