A multiscale model for avascular tumor growth.
The desire to understand tumor complexity has given rise to mathematical models to describe the tumor microenvironment. We present 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 promoters and inhibitors have diffusion coefficients in the range between 10(-6) and 10(-7) cm2/h, corresponding to molecules of size 80-90 kDa. Using the same parameters, the model also accurately predicts spheroid growth curves under different external nutrient supply conditions.
Jiang
Yi
Y
Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA. jiang@lanl.gov
Pjesivac-Grbovic
Jelena
J
Cantrell
Charles
C
Freyer
James P
JP
D000818:Animals; D002448:Cell Adhesion; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D003198:Computer Simulation; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology*; D051379:Mice; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D018874:Spheroids, Cellular / Q000502:physiology*