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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

Number of proliferating non-stem cancer generalized cells as a function of time.The number of proliferating non-stem cancer generalized cells saturates and even to decrease when most generalized cells are able to invade the stromal tissue, forming numerous tumor small clusters.
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pone.0127972.g008: Number of proliferating non-stem cancer generalized cells as a function of time.The number of proliferating non-stem cancer generalized cells saturates and even to decrease when most generalized cells are able to invade the stromal tissue, forming numerous tumor small clusters.

Mentions: The number and fraction of generalized cells of each type changes with time. The number of Necrotic generalized cells increases as the cluster grows, then decreases once generalized cells begin to invade the surrounding tissue, see Fig 5. For Pm = 0.1, δam = 0.5 and for Pm = 0.1, δam = 1.0 the number of Necrotic generalized cells decreases slowly, while for other combinations of Pm and δam the number of Necrotic generalized cells decreases rapidly. A cluster must contain at least one stem-like generalized cell to survive, so we expect the fraction of stem-like generalized cells to increase as the number of clusters increases and the cluster size decreases. The number of stem-like generalized cells increases continuously. For Pm = 0.1, δam = 0.5 and Pm = 0.1, δam = 1.0 the number of stem-like generalized cells increases more slowly than for other combinations of parameters (see Figs. 6 and 7). As more generalized cells develop an invasive phenotype, the initial cluster gives way to many smaller clusters. Because these clusters are small, almost all generalized cells receive sufficient glucose and the number of necrotic generalized cells decreases as the number of proliferating non-stem cancer generalized cells begins to saturate (see Fig 8). We see a clear distinction if we compare the numbers of quiescent (Fig 9) and proliferating (Fig 8) non-stem cancer generalized cells. Both saturate and begin to decrease, the former as soon as a few generalized cells establish new clusters, the latter only when small clusters fill the entire tissue.


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)

Number of proliferating non-stem cancer generalized cells as a function of time.The number of proliferating non-stem cancer generalized cells saturates and even to decrease when most generalized cells are able to invade the stromal tissue, forming numerous tumor small clusters.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0127972.g008: Number of proliferating non-stem cancer generalized cells as a function of time.The number of proliferating non-stem cancer generalized cells saturates and even to decrease when most generalized cells are able to invade the stromal tissue, forming numerous tumor small clusters.
Mentions: The number and fraction of generalized cells of each type changes with time. The number of Necrotic generalized cells increases as the cluster grows, then decreases once generalized cells begin to invade the surrounding tissue, see Fig 5. For Pm = 0.1, δam = 0.5 and for Pm = 0.1, δam = 1.0 the number of Necrotic generalized cells decreases slowly, while for other combinations of Pm and δam the number of Necrotic generalized cells decreases rapidly. A cluster must contain at least one stem-like generalized cell to survive, so we expect the fraction of stem-like generalized cells to increase as the number of clusters increases and the cluster size decreases. The number of stem-like generalized cells increases continuously. For Pm = 0.1, δam = 0.5 and Pm = 0.1, δam = 1.0 the number of stem-like generalized cells increases more slowly than for other combinations of parameters (see Figs. 6 and 7). As more generalized cells develop an invasive phenotype, the initial cluster gives way to many smaller clusters. Because these clusters are small, almost all generalized cells receive sufficient glucose and the number of necrotic generalized cells decreases as the number of proliferating non-stem cancer generalized cells begins to saturate (see Fig 8). We see a clear distinction if we compare the numbers of quiescent (Fig 9) and proliferating (Fig 8) non-stem cancer generalized cells. Both saturate and begin to decrease, the former as soon as a few generalized cells establish new clusters, the latter only when small clusters fill the entire tissue.

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