A MULTISCALE MODEL FOR AVASCULAR TUMOR GROWTH

Los Alamos Nat Secty-Los Alamos Nat Lab, Los Alamos NM

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The desire to understand tumor complexity has given rise to mathematical models to describe the tumor microenvironment. We have developed a new mathematical model for avascular tumor growth and development that spans three distinct scales. At the cellular level, a lattice Monte Carlo model describes cellular dynamics (proliferation, adhesion and viability). At the subcellular level, a Boolean network regulates the expression of proteins that control the cell cycle. At the extracellular level, reaction-diffusion equations describe the chemical dynamics (nutrient, waste, growth promoter and inhibitor concentrations). Data from experiments with multicellular spheroids were used to determine the parameters of the simulations. Starting with a single tumor cell, this model produces an avascular tumor that quantitatively mimics experimental measurements in multicellular spheroids. Based on the simulations, we predict: 1) the microenvironmental conditions required for tumor cell survival;and 2) growth promotors and inhibitors have diffusion coefficients in the range between 10-6 and 10-7 cm2/hr, corresponding to molecules of size 80-90 kD. Using the same parameters, the model also accurately predicts spheroid growth curves under different external nutrient supply conditions.