Multiscale modelling of vascular tumour growth in 3D: the roles of domain size and boundary conditions.

We investigate a three-dimensional multiscale model of vascular tumour growth, which couples blood flow, angiogenesis, vascular remodelling, nutrient/growth factor transport, movement of, and interactions between, normal and tumour cells, and nutrient-dependent cell cycle dynamics within each cell....

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Main Authors: Holger Perfahl, Helen M Byrne, Tingan Chen, Veronica Estrella, Tomás Alarcón, Alexei Lapin, Robert A Gatenby, Robert J Gillies, Mark C Lloyd, Philip K Maini, Matthias Reuss, Markus R Owen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-04-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3076378?pdf=render
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author Holger Perfahl
Helen M Byrne
Tingan Chen
Veronica Estrella
Tomás Alarcón
Alexei Lapin
Robert A Gatenby
Robert J Gillies
Mark C Lloyd
Philip K Maini
Matthias Reuss
Markus R Owen
author_facet Holger Perfahl
Helen M Byrne
Tingan Chen
Veronica Estrella
Tomás Alarcón
Alexei Lapin
Robert A Gatenby
Robert J Gillies
Mark C Lloyd
Philip K Maini
Matthias Reuss
Markus R Owen
author_sort Holger Perfahl
collection DOAJ
description We investigate a three-dimensional multiscale model of vascular tumour growth, which couples blood flow, angiogenesis, vascular remodelling, nutrient/growth factor transport, movement of, and interactions between, normal and tumour cells, and nutrient-dependent cell cycle dynamics within each cell. In particular, we determine how the domain size, aspect ratio and initial vascular network influence the tumour's growth dynamics and its long-time composition. We establish whether it is possible to extrapolate simulation results obtained for small domains to larger ones, by constructing a large simulation domain from a number of identical subdomains, each subsystem initially comprising two parallel parent vessels, with associated cells and diffusible substances. We find that the subsystem is not representative of the full domain and conclude that, for this initial vessel geometry, interactions between adjacent subsystems contribute to the overall growth dynamics. We then show that extrapolation of results from a small subdomain to a larger domain can only be made if the subdomain is sufficiently large and is initialised with a sufficiently complex vascular network. Motivated by these results, we perform simulations to investigate the tumour's response to therapy and show that the probability of tumour elimination in a larger domain can be extrapolated from simulation results on a smaller domain. Finally, we demonstrate how our model may be combined with experimental data, to predict the spatio-temporal evolution of a vascular tumour.
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spelling doaj.art-7c38252c1ae64071ac049093438893c72022-12-22T02:01:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-04-0164e1479010.1371/journal.pone.0014790Multiscale modelling of vascular tumour growth in 3D: the roles of domain size and boundary conditions.Holger PerfahlHelen M ByrneTingan ChenVeronica EstrellaTomás AlarcónAlexei LapinRobert A GatenbyRobert J GilliesMark C LloydPhilip K MainiMatthias ReussMarkus R OwenWe investigate a three-dimensional multiscale model of vascular tumour growth, which couples blood flow, angiogenesis, vascular remodelling, nutrient/growth factor transport, movement of, and interactions between, normal and tumour cells, and nutrient-dependent cell cycle dynamics within each cell. In particular, we determine how the domain size, aspect ratio and initial vascular network influence the tumour's growth dynamics and its long-time composition. We establish whether it is possible to extrapolate simulation results obtained for small domains to larger ones, by constructing a large simulation domain from a number of identical subdomains, each subsystem initially comprising two parallel parent vessels, with associated cells and diffusible substances. We find that the subsystem is not representative of the full domain and conclude that, for this initial vessel geometry, interactions between adjacent subsystems contribute to the overall growth dynamics. We then show that extrapolation of results from a small subdomain to a larger domain can only be made if the subdomain is sufficiently large and is initialised with a sufficiently complex vascular network. Motivated by these results, we perform simulations to investigate the tumour's response to therapy and show that the probability of tumour elimination in a larger domain can be extrapolated from simulation results on a smaller domain. Finally, we demonstrate how our model may be combined with experimental data, to predict the spatio-temporal evolution of a vascular tumour.http://europepmc.org/articles/PMC3076378?pdf=render
spellingShingle Holger Perfahl
Helen M Byrne
Tingan Chen
Veronica Estrella
Tomás Alarcón
Alexei Lapin
Robert A Gatenby
Robert J Gillies
Mark C Lloyd
Philip K Maini
Matthias Reuss
Markus R Owen
Multiscale modelling of vascular tumour growth in 3D: the roles of domain size and boundary conditions.
PLoS ONE
title Multiscale modelling of vascular tumour growth in 3D: the roles of domain size and boundary conditions.
title_full Multiscale modelling of vascular tumour growth in 3D: the roles of domain size and boundary conditions.
title_fullStr Multiscale modelling of vascular tumour growth in 3D: the roles of domain size and boundary conditions.
title_full_unstemmed Multiscale modelling of vascular tumour growth in 3D: the roles of domain size and boundary conditions.
title_short Multiscale modelling of vascular tumour growth in 3D: the roles of domain size and boundary conditions.
title_sort multiscale modelling of vascular tumour growth in 3d the roles of domain size and boundary conditions
url http://europepmc.org/articles/PMC3076378?pdf=render
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