title: Emergent Stratification in Solid Tumors Selects for Reduced Cohesion of Tumor Cells: A Multi-Cell, Virtual-Tissue Model of Tumor Evolution Using CompuCell3D.
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.
authors.affiliation: Biocomplexity Institute and Department of Physics, Indiana University, Bloomington, Indiana, USA.
authors.forename: Maciej H
authors.initials: MH
authors.lastname: Swat
authors.affiliation: Instituto de Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Gilberto L
authors.initials: GL
authors.lastname: Thomas
authors.affiliation: St. Jude Children's Research Hospital, Department of Information Sciences, Division of Clinical Informatics, Memphis, USA.
authors.forename: Abbas
authors.initials: A
authors.lastname: Shirinifard
authors.affiliation: Biocomplexity Institute and Department of Physics, Indiana University, Bloomington, Indiana, USA.
authors.forename: Sherry G
authors.initials: SG
authors.lastname: Clendenon
authors.affiliation: Biocomplexity Institute and Department of Physics, Indiana University, Bloomington, Indiana, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Glazier
mesh_terms: D000465:Algorithms; D002448:Cell Adhesion; D016922:Cellular Senescence; D005947:Glucose / Q000378:metabolism; D006801:Humans; D020407:Internet; D008938:Mitosis; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D014584:User-Computer Interface
chemical_list: D005947:Glucose