Mathematical modeling of tumor-microenvironment dynamics

In this thesis we explore tumor-microenvironment dynamics using three models of decreasing complexity. The first is a multispecies, spatiotemporal model of tumor development in tumor-derived growth factor responsive stroma that is activated to secrete the tumor growth and dispersal activator HGF. We show that HGF-induced invasive tumor morphology is promoted by increased heterogeneity at the tumor-host boundary. The second model is a system of ODEs that explores hypotheses based on experimental observations that tumor growth inhibition can occur at high levels of HGF. The model allows for the prediction of the molecular mechanism of HGF action via dose-response curve analysis. The final model is a system of two ODEs for stem cell and chemical activator of stem cell self-renewal concentrations, and allows for the approximation of the separatrix of the phase space that divides the space into basins of attraction for tumor eradication and tumor maintenance. The multiple models allow us to consider tumor-host interactions at various levels of abstraction and thus to infer both qualitative and quantitative results regarding tumor response to host and tumor-derived growth activators.