Emergent Properties of Tumor Microenvironment in a Real-life Model of Multicell Tumor Spheroids

TL;DR

This study introduces a biophysical computational model of multicellular tumor spheroids that simulates internal tumor microenvironment dynamics, providing insights into tumor development and potential therapeutic targets.

Contribution

A novel computer program integrating cellular behavior and interactions to model tumor spheroid microenvironments at a detailed biophysical level.

Findings

Reproduces experimental data on spheroids

Reveals complex internal flows and motions

Provides new insights into tumor development

Abstract

Multicellular tumor spheroids are an important {\it in vitro} model of the pre-vascular phase of solid tumors, for sizes well below the diagnostic limit: therefore a biophysical model of spheroids has the ability to shed light on the internal workings and organization of tumors at a critical phase of their development. To this end, we have developed a computer program that integrates the behavior of individual cells and their interactions with other cells and the surrounding environment. It is based on a quantitative description of metabolism, growth, proliferation and death of single tumor cells, and on equations that model biochemical and mechanical cell-cell and cell-environment interactions. The program reproduces existing experimental data on spheroids, and yields unique views of their microenvironment. Simulations show complex internal flows and motions of nutrients, metabolites and cells, that are otherwise unobservable with current experimental techniques, and give novel clues on tumor development and strong hints for future therapies.