Mathematical model for cell competition: Predator–prey interactions at the interface between two groups of cells in monolayer tissue

Nishikawa, Seiya; Takamatsu, Atsuko; Ohsawa, Seiji; Igaki, Tatsushi

doi:10.1016/j.jtbi.2016.05.031

Cited by 17 publications

(14 citation statements)

References 30 publications

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“…(14), which would lead to v front being weighted differently in Eq. (18), and to different values of the model-dependent relative parameters. Over longer time scales, tissue material parameters may become time-dependent [20,34], and differences in cell proliferation rates may become relevant [15].…”

Section: Discussionmentioning

confidence: 99%

Collective stresses drive competition between monolayers of normal and Ras-transformed cells

et al. 2019

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We study the competition for space between two cell lines that differ only in the expression of the Ras oncogene. The two cell populations are initially separated and set to migrate antagonistically towards an in-between stripe of free substrate. After contact, their interface moves towards the population of normal cells. We interpret the velocity and traction force data taken before and after contact thanks to a hydrodynamic description of collectively migrating cohesive cell sheets. The kinematics of cells, before and after contact, allows us to estimate the relative material parameters for both cell lines. As predicted by the model, the transformed cell population with larger collective stresses pushes the wild type cell population.

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Section: Discussionmentioning

confidence: 99%

Collective stresses drive competition between monolayers of normal and Ras-transformed cells

et al. 2019

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“…The MDA-MB-231 cells, on the other hand, formed the spheroid or tumor edge by extending their range outward beyond that of the MCF-7 cells. This same pattern, where cells on the periphery of a tumor leave an open niche for another cell type in the interior, has been shown experimentally and also analyzed using Lotka-Volterra competition equations in the Drosophila imaginal disc (41–43).…”

Section: Discussionmentioning

confidence: 53%

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

Freischel

Damaghi

Cunningham

et al. 2020

Preprint

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Highlights: 15 • Demonstrate how mixed-culture spheroids must be used to characterize competition 16 between two cancer cell lines. 17 • Competition alters growth dynamics of cancer cells. 18 • Competition growth models can be used to quantify density-independent, density-19 dependent and frequency-dependent effects on competition. 20 • Competition affects tumor progression and structure, making it key to understanding 21 tumor development and evolution. 22 ABSTRACT: 23Tumors are highly dynamic ecosystems in which diverse cancer cell subpopulations compete for space 24 and resources. These complex, often non-linear interactions govern continuous spatial and temporal 25 changes in the size and phenotypic properties of these subpopulations. Because intra-tumoral blood 26 flow is often chaotic, competition for resources may be a critical selection factor in progression and 27 prognosis. Here, we quantify resource competition using 3D spheroid cultures with MDA-MB-231 and 28 MCF-7 breast cancer cells. We hypothesized that MCF-7 cells, which primarily rely on efficient aerobic 29 glucose metabolism, would then dominate the population under normoxic conditions; and MDA-MB-30 231 cells, which exhibit high levels of glycolytic metabolism, would dominate under hypoxic conditions. 31In spheroids with single populations, MCF-7 cells exhibited equal or superior intrinsic growth rates 32 (density-independent measure of success) and carrying capacities (density-dependent measure of 33 success) when compared to MDA-MB-231 cells in both normoxic and hypoxic conditions. However, 34 when the populations were mixed, MDA-MB-231 cells outcompeted MCF-7 cells under all conditions 35 with competition dynamics determined by frequency-dependent interactions. When grown together, 36 MDA-MB-231 suffered little from MCF-7 while MCF-7 cells experienced a disproportionately large 37 reduction in growth rates in the presence of MDA-MB-231 cells. We frame these results in a game-38 theoretic (frequency-dependent) model of cancer cell interactions and conclude that competition assays 39 can demonstrate critical density-independent, density-dependent and frequency-dependent 40 interactions that likely contribute to in vivo outcomes. 41Key Words: cancer cell competition, tumor ecology, tumor evolution, evolutionary therapy 42 43 INTRODUCTION: 44Each malignant tumor typically contains diverse and heterogeneous habitats due to spatial and temporal 45 variations in cell density, immune infiltration, and blood flow (1-3). Here, we investigate the 46 evolutionary effects of variations in substrate (e.g. glucose, oxygen, and glutamine) and metabolites 47Recently, two general "niche construction" strategies were observed in clinical and pre-clinical cancers 51 (4, 5). The first consists of cancer cells that possess high levels of aerobic glycolysis that generate an 52 acidic environment which promotes invasion and protects cells from the immune system. These cells are 53 typically invasive and motile. In the second niche construction strat...

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“…Previous studies have introduced the concept of fitness to discuss the intensity of cell competition [ 8 , 37 , 38 ]. The main focus was relative survivability, that is, which population survives when different populations with different genetic backgrounds are mixed.…”

Section: Resultsmentioning

confidence: 99%

Possible roles of mechanical cell elimination intrinsic to growing tissues from the perspective of tissue growth efficiency and homeostasis

Lee¹,

Morishita²

2017

PLoS Comput Biol

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Cell competition is a phenomenon originally described as the competition between cell populations with different genetic backgrounds; losing cells with lower fitness are eliminated. With the progress in identification of related molecules, some reports described the relevance of cell mechanics during elimination. Furthermore, recent live imaging studies have shown that even in tissues composed of genetically identical cells, a non-negligible number of cells are eliminated during growth. Thus, mechanical cell elimination (MCE) as a consequence of mechanical cellular interactions is an unavoidable event in growing tissues and a commonly observed phenomenon. Here, we studied MCE in a genetically-homogeneous tissue from the perspective of tissue growth efficiency and homeostasis. First, we propose two quantitative measures, cell and tissue fitness, to evaluate cellular competitiveness and tissue growth efficiency, respectively. By mechanical tissue simulation in a pure population where all cells have the same mechanical traits, we clarified the dependence of cell elimination rate or cell fitness on different mechanical/growth parameters. In particular, we found that geometrical (specifically, cell size) and mechanical (stress magnitude) heterogeneities are common determinants of the elimination rate. Based on these results, we propose possible mechanical feedback mechanisms that could improve tissue growth efficiency and density/stress homeostasis. Moreover, when cells with different mechanical traits are mixed (e.g., in the presence of phenotypic variation), we show that MCE could drive a drastic shift in cell trait distribution, thereby improving tissue growth efficiency through the selection of cellular traits, i.e. intra-tissue “evolution”. Along with the improvement of growth efficiency, cell density, stress state, and phenotype (mechanical traits) were also shown to be homogenized through growth. More theoretically, we propose a mathematical model that approximates cell competition dynamics, by which the time evolution of tissue fitness and cellular trait distribution can be predicted without directly simulating a cell-based mechanical model.

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Mathematical model for cell competition: Predator–prey interactions at the interface between two groups of cells in monolayer tissue

Cited by 17 publications

References 30 publications

Collective stresses drive competition between monolayers of normal and Ras-transformed cells

Collective stresses drive competition between monolayers of normal and Ras-transformed cells

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

Possible roles of mechanical cell elimination intrinsic to growing tissues from the perspective of tissue growth efficiency and homeostasis

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