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In Silico Biology 2, 0035 (2002); ©2002, Bioinformation Systems e.V.  

Modeling of self-organized avascular tumor growth with a hybrid cellular automaton

Sabine Dormann1 and Andreas Deutsch2,*

1Inst. of Environmental Systems Research, University of Osnabrück, D-49069 Osnabrück,
2Center for High Performance Computing (ZHR), Dresden University of Technology, D-01062 Dresden,

*Corresponding author

Edited by E. Wingender; received December 13, 2001; revised and accepted February 6, 2002; published April 13, 2002


Pattern formation in multicellular spheroids is addressed with a hybrid lattice-gas cellular automaton model. Multicellular spheroids serve as experimental model system for the study of avascular tumor growth. Typically, multicellular spheroids consist of a necrotic core surrounded by rings of quiescent and proliferating tumor cells, respectively. Furthermore, after an initial exponential growth phase further spheroid growth is significantly slowed down even if further nutrient is supplied. The cellular automaton model explicitly takes into account mitosis, apoptosis and necrosis as well as nutrient consumption and a diffusible signal that is emitted by cells becoming necrotic. All cells follow identical interaction rules. The necrotic signal induces a chemotactic migration of tumor cells towards maximal signal concentrations. Starting from a small number of tumor cells automaton simulations exhibit the self-organized formation of a layered structure consisting of a necrotic core, a ring of quiescent tumor cells and a thin outer ring of proliferating tumor cells.

Key words: avascular tumor growth, multicellular spheroid, mathematical model, simulation, cellular automaton, self-organization