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Emergent Stratification in Solid Tumors Selects for Reduced Cohesion of Tumor Cells: A Multi-Cell, Virtual-Tissue Model of Tumor Evolution Using CompuCell3D.

Swat MH, Thomas GL, Shirinifard A, Clendenon SG, Glazier JA - PLoS ONE (2015)

Bottom Line: Our model includes essential cell behaviors, microenvironmental components and their interactions.Our model provides a platform for exploring selection pressures leading to the evolution of tumor-cell aggression, showing that emergent stratification into regions with different cell survival rates drives the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins.Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors.

View Article: PubMed Central - PubMed

Affiliation: Biocomplexity Institute and Department of Physics, Indiana University, Bloomington, Indiana, USA.

ABSTRACT
Tumor cells and structure both evolve due to heritable variation of cell behaviors and selection over periods of weeks to years (somatic evolution). Micro-environmental factors exert selection pressures on tumor-cell behaviors, which influence both the rate and direction of evolution of specific behaviors, especially the development of tumor-cell aggression and resistance to chemotherapies. In this paper, we present, step-by-step, the development of a multi-cell, virtual-tissue model of tumor somatic evolution, simulated using the open-source CompuCell3D modeling environment. Our model includes essential cell behaviors, microenvironmental components and their interactions. Our model provides a platform for exploring selection pressures leading to the evolution of tumor-cell aggression, showing that emergent stratification into regions with different cell survival rates drives the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins. Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors.

No MeSH data available.


Related in: MedlinePlus

A) Model cell-state transitions as a function of the glucose supply. As implemented in the simulation: (B) Flowchart for (Q)uiescent (S or C) cell transitions; (C) Flowchart for (P)roliferative (C)ancer cell transitions; (D) Flowchart for (P)roliferative (S)tem cell transitions.
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pone.0127972.g001: A) Model cell-state transitions as a function of the glucose supply. As implemented in the simulation: (B) Flowchart for (Q)uiescent (S or C) cell transitions; (C) Flowchart for (P)roliferative (C)ancer cell transitions; (D) Flowchart for (P)roliferative (S)tem cell transitions.

Mentions: Real quiescent tumor cells become proliferative only when they experience sufficient levels of nutrients for long enough periods (refractory behavior) [3]. We model this refractory behavior of individual quiescent-state tumor cells by requiring them to accumulate health, which biologically corresponds to repair of damage due to hypoxia or other harsh microenvironmental conditions. Cells that experience higher nutrient concentrations accumulate health at a faster rate, which saturates for high nutrient concentrations. Fig 1 shows how glucose supply induces transitions between model cell states and presents related flowcharts for the simulation code.


Emergent Stratification in Solid Tumors Selects for Reduced Cohesion of Tumor Cells: A Multi-Cell, Virtual-Tissue Model of Tumor Evolution Using CompuCell3D.

Swat MH, Thomas GL, Shirinifard A, Clendenon SG, Glazier JA - PLoS ONE (2015)

A) Model cell-state transitions as a function of the glucose supply. As implemented in the simulation: (B) Flowchart for (Q)uiescent (S or C) cell transitions; (C) Flowchart for (P)roliferative (C)ancer cell transitions; (D) Flowchart for (P)roliferative (S)tem cell transitions.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4470639&req=5

pone.0127972.g001: A) Model cell-state transitions as a function of the glucose supply. As implemented in the simulation: (B) Flowchart for (Q)uiescent (S or C) cell transitions; (C) Flowchart for (P)roliferative (C)ancer cell transitions; (D) Flowchart for (P)roliferative (S)tem cell transitions.
Mentions: Real quiescent tumor cells become proliferative only when they experience sufficient levels of nutrients for long enough periods (refractory behavior) [3]. We model this refractory behavior of individual quiescent-state tumor cells by requiring them to accumulate health, which biologically corresponds to repair of damage due to hypoxia or other harsh microenvironmental conditions. Cells that experience higher nutrient concentrations accumulate health at a faster rate, which saturates for high nutrient concentrations. Fig 1 shows how glucose supply induces transitions between model cell states and presents related flowcharts for the simulation code.

Bottom Line: Our model includes essential cell behaviors, microenvironmental components and their interactions.Our model provides a platform for exploring selection pressures leading to the evolution of tumor-cell aggression, showing that emergent stratification into regions with different cell survival rates drives the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins.Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors.

View Article: PubMed Central - PubMed

Affiliation: Biocomplexity Institute and Department of Physics, Indiana University, Bloomington, Indiana, USA.

ABSTRACT
Tumor cells and structure both evolve due to heritable variation of cell behaviors and selection over periods of weeks to years (somatic evolution). Micro-environmental factors exert selection pressures on tumor-cell behaviors, which influence both the rate and direction of evolution of specific behaviors, especially the development of tumor-cell aggression and resistance to chemotherapies. In this paper, we present, step-by-step, the development of a multi-cell, virtual-tissue model of tumor somatic evolution, simulated using the open-source CompuCell3D modeling environment. Our model includes essential cell behaviors, microenvironmental components and their interactions. Our model provides a platform for exploring selection pressures leading to the evolution of tumor-cell aggression, showing that emergent stratification into regions with different cell survival rates drives the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins. Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors.

No MeSH data available.


Related in: MedlinePlus