Deterministic and stochastic aspects of VEGF-A production and the cooperative behavior of tumoral cell colony

TL;DR

This paper presents a model of hypoxia-induced angiogenesis in cancer cells, focusing on VEGF-A regulation by HIF-1alpha, analyzing deterministic and stochastic effects, and revealing cooperative behaviors among tumor cells.

Contribution

It introduces a novel model combining deterministic and stochastic dynamics of VEGF-A production and tumor cell cooperation under hypoxia conditions.

Findings

Distinct behaviors under normoxia, hypoxia, and cell death regimes.

Stochastic fluctuations induce cooperative interactions among tumor cells.

Model highlights the role of molecular regulation in tumor angiogenesis.

Abstract

A model is proposed to study the process of hypoxia-induced angiogenesis in cancer cells. The model accounts for the role played by the vascular endothelial growth factor (VEGF)-A in regulating the oxygen intake. VEGF-A is dynamically controlled by the HIF-1alpha concentration. If not degraded, HIF-1alpha can bind to the subunit termed HIF-1beta and so experience translocation to the nucleus, to exert its proper transcriptional activity. The delicate balance between these opposing tendencies translates into the emergence of distinct macroscopic behaviors in terms of the associated molecular concentrations that we here trace back to normoxia, hypoxia and death regimes. These aspects are firstly analyzed with reference to the ideal mean-field scenario. Stochastic fluctuations are also briefly discussed and shown to seed a cooperative interaction among cellular units, competing for the same oxygen reservoir.