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Multicellular tumor spheroids are an important {\it in vitro} model of thepre-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 theinternal workings and organization of tumors at a critical phase of theirdevelopment. To this end, we have developed a computer program that integratesthe behavior of individual cells and their interactions with other cells andthe surrounding environment. It is based on a quantitative description ofmetabolism, growth, proliferation and death of single tumor cells, and onequations that model biochemical and mechanical cell-cell and cell-environmentinteractions. The program reproduces existing experimental data on spheroids,and yields unique views of their microenvironment. Simulations show complexinternal flows and motions of nutrients, metabolites and cells, that areotherwise unobservable with current experimental techniques, and give novelclues on tumor development and strong hints for future therapies.

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