The impact of proliferation-migration tradeoffs on phenotypic evolution in cancer

Scientific Reports
Jill GallaherAlexander R A Anderson

Abstract

Tumors are not static masses of cells but 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, and (4) whether deaths occur in response to demographic or environmental stochasticity. Using a spatially-explicit agent-based model, we observe how two traits (proliferation rate and migration speed) evolve under different tradeoff conditions with different turnover rates. Migration rate is favored over proliferation at the tumor's edge and vice-versa for the interior. Increasing cell turnover rates slightly slows tumor growth but accelerates the rate of evolution for both proliferation and migration. The absence of a tradeoff favors ever higher values for proliferation and migration, while a convex tradeoff tends to favor proliferation, often promoting the coexistence of a generalist and specialist phenotype. A concave tradeoff favors migration at low death rates, but switches to proliferation at higher death rates. Mortality via demographic stochasticity favors proliferation, and environmental stochasticity favors migration...Continue Reading

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Citations

Oct 3, 2019·Scientific Reports·Cindy MendesJacinta Serpa
Jun 26, 2020·Cancers·Kambiz AfrasiabiYi-Hong Zhou
Feb 26, 2020·Nature Reviews. Cancer·Jean Hausser, Uri Alon
Jun 20, 2020·Bulletin of Mathematical Biology·Aleksandra ArdaševaTommaso Lorenzi
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Jan 27, 2021·Integrative Biology : Quantitative Biosciences From Nano to Macro·Emann M RabieCeleste M Nelson
Nov 2, 2019·Gene·Saif F KhanSharon Prince
Mar 9, 2021·Biomechanics and Modeling in Mechanobiology·Yaniv Ben-David, Daphne Weihs
Mar 19, 2021·British Journal of Cancer·Matthew DeyellAshley M Laughney
Mar 14, 2021·Journal of Mathematical Biology·Sean T VittadelloMatthew J Simpson
Mar 25, 2021·Mathematical Biosciences·Marisabel Rodriguez MessanDorothy Wallace
Apr 8, 2021·Nature Communications·Jeffrey WestAlexander R A Anderson
Jun 16, 2021·Bulletin of Mathematical Biology·Giada FiandacaTommaso Lorenzi
Nov 30, 2021·PLoS Computational Biology·Ernesto A B F LimaThomas E Yankeelov

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Methods Mentioned

BETA
biopsies

Software Mentioned

MATLAB
Pixelmator

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