Microenvironmental cooperation promotes early spread and bistability of a Warburg-like phenotype

Abstract

We introduce an in silico model for the initial spread of an aberrant phenotype with Warburg-like overflow metabolism within a healthy homeostatic tissue in contact with a nutrient reservoir (the blood), aimed at characterizing the role of the microenvironment for aberrant growth. Accounting for cellular metabolic activity, competition for nutrients, spatial diffusion and their feedbacks on aberrant replication and death rates, we obtain a phase portrait where distinct asymptotic whole-tissue states are found upon varying the tissue-blood turnover rate and the level of blood-borne primary nutrient. Over a broad range of parameters, the spreading dynamics is bistable as random fluctuations can impact the final state of the tissue. Such a behaviour turns out to be linked to the re-cycling of overflow products by non-aberrant cells. Quantitative insight on the overall emerging picture is provided by a spatially homogeneous version of the model.

14 pages

References in corpus (4)

• Constrained Allocation Flux Balance Analysis
• Quantitative constraint-based computational model of tumor-to-stroma coupling via lactate shuttle
• Dynamical instabilities in a simple minority game with discounting
• Inferring metabolic phenotypes from the exometabolome through a thermodynamic variational principle

Cited by in corpus (4)

• Characterizing steady states of genome-scale metabolic networks in continuous cell cultures
• Maximum entropy and population heterogeneity in continuous cell cultures
• Spin Glass Theory of Interacting Metabolic Networks
• Metabolic coordination and phase transitions in spatially distributed multi-cellular systems