The dynamic tumor ecosystem: how cell turnover and trade-offs affect cancer evolution

Abstract

AO_SCPCAPBSTRACTC_SCPCAPTumors are not static masses of cells but rather dynamic ecosystems where cancer cells experience constant turnover and evolve fitness-enhancing phenotypes. Selection for different phenotypes may vary with 1) the tumor niche (edge or core), 2) cell turnover rates, 3) the nature of the tradeoff between traits (proliferation vs migration), and 4) whether deaths occur in response to demographic or environmental stochasticity. In an agent based, spatially-explicit model, we observe how two traits (proliferation rate and migration speed) evolve under different trade-off conditions with different turnover rates. Migration rate is favored over proliferation at the tumors edge and vice-versa for the interior. Increasing cell turnover rates only slightly slows the growth of the tumor, but accelerates the rate of evolution for both proliferation and migration. The absence of a tradeoff favors ever higher values for proliferation and migration. A convex tradeoff tends to favor proliferation over migration while often promoting the coexistence of a generalist and specialist phenotype. A concave tradeoff slows the rate of evolution, and favors migration at low death rates and proliferation at higher death rates. Mortality via demographic stochasticity favors proliferation at the expense of migration; and vice-versa for environmental stochasticity. All of these factors and their interactions contribute to the ecology of the tumor, tumor heterogeneity, trait evolution, and phenotypic variation. While diverse, these effects may be predictable and empirically accessible.