Evolution of cell motility in an individual-based model of tumour growth
Authored by P Gerlee, A R A Anderson
Date Published: 2009
DOI: 10.1016/j.jtbi.2009.03.005
Sponsors:
National Cancer Institute
Platforms:
No platforms listed
Model Documentation:
Other Narrative
Flow charts
Mathematical description
Model Code URLs:
Model code not found
Abstract
Tumour invasion is driven by proliferation and importantly migration
into the surrounding tissue. Cancer cell motility is also critical in
the formation of metastases and is therefore a fundamental issue in
cancer research. In this paper we investigate the emergence of cancer
cell motility in an evolving turnout population using an
individual-based modelling approach. In this model of turnout growth
each cell is equipped with a micro-environment response network that
determines the behaviour or phenotype of the cell based on the local
environment. The response network is modelled using a feed-forward
neural network, which is subject to mutations when the cells divide.
With this model we have investigated the impact of the micro-environment
on the emergence of a motile invasive phenotype. The results show that
when a motile phenotype emerges the dynamics of the model are radically
changed and we observe faster growing tumours exhibiting diffuse
morphologies. Further we observe that the emergence of a motile subclone
can occur in a wide range of micro-environmental growth conditions.
Iterated simulations showed that in identical growth conditions the
evolutionary dynamics either converge to a proliferating or migratory
phenotype, which suggests that the introduction of cell motility into
the model changes the shape of fitness landscape on which the cancer
cell population evolves and that it now contains several local maxima.
This could have important implications for cancer treatments which focus
on the gene level, as our results show that several distinct genotypes
and critically distinct phenotypes can emerge and become dominant in the
same micro-environment. (C) 2008 Elsevier Ltd. All rights reserved.
Tags
invasion
Extracellular-matrix
Game-theory
Computational-model
Clonal expansion
Adhesion
Multicellular spheroids
Cancer initiation
Automaton
model
Nonlinear simulation