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

TL;DR

This study models how microenvironmental factors influence the early spread and bistability of Warburg-like metabolic phenotypes in tissues, highlighting the role of nutrient competition and cellular recycling in aberrant growth dynamics.

Contribution

It introduces a novel in silico model that captures the microenvironment's impact on the initial spread of Warburg-like phenotypes in tissue, revealing bistability and the influence of nutrient recycling.

Findings

Bistable spreading dynamics influenced by nutrient levels.

Microenvironmental recycling promotes aberrant phenotype persistence.

Spatially homogeneous model provides quantitative insights.

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.