Frequency-dependent interactions determine outcome of competition between two breast cancer cell lines

Abstract Tumors are highly dynamic ecosystems in which diverse cancer cell subpopulations compete for space and resources. These complex, often non-linear interactions govern continuous spatial and temporal changes in the size and phenotypic properties of these subpopulations. Because intra-tumoral...

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Autores principales:	Audrey R. Freischel, Mehdi Damaghi, Jessica J. Cunningham, Arig Ibrahim-Hashim, Robert J. Gillies, Robert A. Gatenby, Joel S. Brown
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f0f4b0c70bab455b9fc67a0de7c54b2e
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spelling	oai:doaj.org-article:f0f4b0c70bab455b9fc67a0de7c54b2e2021-12-02T13:34:46ZFrequency-dependent interactions determine outcome of competition between two breast cancer cell lines10.1038/s41598-021-84406-32045-2322https://doaj.org/article/f0f4b0c70bab455b9fc67a0de7c54b2e2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84406-3https://doaj.org/toc/2045-2322Abstract Tumors are highly dynamic ecosystems in which diverse cancer cell subpopulations compete for space and resources. These complex, often non-linear interactions govern continuous spatial and temporal changes in the size and phenotypic properties of these subpopulations. Because intra-tumoral blood flow is often chaotic, competition for resources may be a critical selection factor in progression and prognosis. Here, we quantify resource competition using 3D spheroid cultures with MDA-MB-231 and MCF-7 breast cancer cells. We hypothesized that MCF-7 cells, which primarily rely on efficient aerobic glucose metabolism, would dominate the population under normal pH and low glucose conditions; and MDA-MB-231 cells, which exhibit high levels of glycolytic metabolism, would dominate under low pH and high glucose conditions. In spheroids with single populations, MCF-7 cells exhibited equal or superior intrinsic growth rates (density-independent measure of success) and carrying capacities (density-dependent measure of success) when compared to MDA-MB-231 cells under all pH and nutrient conditions. Despite these advantages, when grown together, MCF-7 cells do not always outcompete MDA-MB-231 cells. MDA-MB-231 cells outcompete MCF-7 cells in low glucose conditions and coexistence is achieved in low pH conditions. Under all conditions, MDA-MB-231 has a stronger competitive effect (frequency-dependent interaction) on MCF-7 cells than vice-versa. This, and the inability of growth rate or carrying capacity when grown individually to predict the outcome of competition, suggests a reliance on frequency-dependent interactions and the need for competition assays. We frame these results in a game-theoretic (frequency-dependent) model of cancer cell interactions and conclude that competition assays can demonstrate critical density-independent, density-dependent and frequency-dependent interactions that likely contribute to in vivo outcomes.Audrey R. FreischelMehdi DamaghiJessica J. CunninghamArig Ibrahim-HashimRobert J. GilliesRobert A. GatenbyJoel S. BrownNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Audrey R. Freischel Mehdi Damaghi Jessica J. Cunningham Arig Ibrahim-Hashim Robert J. Gillies Robert A. Gatenby Joel S. Brown Frequency-dependent interactions determine outcome of competition between two breast cancer cell lines
description	Abstract Tumors are highly dynamic ecosystems in which diverse cancer cell subpopulations compete for space and resources. These complex, often non-linear interactions govern continuous spatial and temporal changes in the size and phenotypic properties of these subpopulations. Because intra-tumoral blood flow is often chaotic, competition for resources may be a critical selection factor in progression and prognosis. Here, we quantify resource competition using 3D spheroid cultures with MDA-MB-231 and MCF-7 breast cancer cells. We hypothesized that MCF-7 cells, which primarily rely on efficient aerobic glucose metabolism, would dominate the population under normal pH and low glucose conditions; and MDA-MB-231 cells, which exhibit high levels of glycolytic metabolism, would dominate under low pH and high glucose conditions. In spheroids with single populations, MCF-7 cells exhibited equal or superior intrinsic growth rates (density-independent measure of success) and carrying capacities (density-dependent measure of success) when compared to MDA-MB-231 cells under all pH and nutrient conditions. Despite these advantages, when grown together, MCF-7 cells do not always outcompete MDA-MB-231 cells. MDA-MB-231 cells outcompete MCF-7 cells in low glucose conditions and coexistence is achieved in low pH conditions. Under all conditions, MDA-MB-231 has a stronger competitive effect (frequency-dependent interaction) on MCF-7 cells than vice-versa. This, and the inability of growth rate or carrying capacity when grown individually to predict the outcome of competition, suggests a reliance on frequency-dependent interactions and the need for competition assays. We frame these results in a game-theoretic (frequency-dependent) model of cancer cell interactions and conclude that competition assays can demonstrate critical density-independent, density-dependent and frequency-dependent interactions that likely contribute to in vivo outcomes.
format	article
author	Audrey R. Freischel Mehdi Damaghi Jessica J. Cunningham Arig Ibrahim-Hashim Robert J. Gillies Robert A. Gatenby Joel S. Brown
author_facet	Audrey R. Freischel Mehdi Damaghi Jessica J. Cunningham Arig Ibrahim-Hashim Robert J. Gillies Robert A. Gatenby Joel S. Brown
author_sort	Audrey R. Freischel
title	Frequency-dependent interactions determine outcome of competition between two breast cancer cell lines
title_short	Frequency-dependent interactions determine outcome of competition between two breast cancer cell lines
title_full	Frequency-dependent interactions determine outcome of competition between two breast cancer cell lines
title_fullStr	Frequency-dependent interactions determine outcome of competition between two breast cancer cell lines
title_full_unstemmed	Frequency-dependent interactions determine outcome of competition between two breast cancer cell lines
title_sort	frequency-dependent interactions determine outcome of competition between two breast cancer cell lines
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f0f4b0c70bab455b9fc67a0de7c54b2e
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Frequency-dependent interactions determine outcome of competition between two breast cancer cell lines

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