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

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 beh...

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Bibliographic Details
Published in:PloS one 2015-06, Vol.10 (6), p.e0127972-e0127972
Main Authors: Swat, Maciej H, Thomas, Gilberto L, Shirinifard, Abbas, Clendenon, Sherry G, Glazier, James A
Format: Article
Language:English
Subjects:
Aggression
Algorithms
Cancer therapies
Cell Adhesion
Cell survival
Cellular Senescence
Chemotherapy
Code reuse
Cohesion
Computer simulation
Environment models
Environmental factors
Evolution
Gangrene
Glucose - metabolism
Growth factors
Humans
Hypoxia
Integrins
Internet
Metastasis
Mitosis
Models, Biological
Motility
Mutation
Neoplasms - metabolism
Neoplasms - pathology
Patients
Physics
Solid tumors
Tumor cells
Tumors
User-Computer Interface
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0127972