The impact of phenotypic switching on glioblastoma growth and invasion.
PLoS Comput Biol
; 8(6): e1002556, 2012.
Article
em En
| MEDLINE
| ID: mdl-22719241
ABSTRACT
The brain tumour glioblastoma is characterised by diffuse and infiltrative growth into surrounding brain tissue. At the macroscopic level, the progression speed of a glioblastoma tumour is determined by two key factors the cell proliferation rate and the cell migration speed. At the microscopic level, however, proliferation and migration appear to be mutually exclusive phenotypes, as indicated by recent in vivo imaging data. Here, we develop a mathematical model to analyse how the phenotypic switching between proliferative and migratory states of individual cells affects the macroscopic growth of the tumour. For this, we propose an individual-based stochastic model in which glioblastoma cells are either in a proliferative state, where they are stationary and divide, or in motile state in which they are subject to random motion. From the model we derive a continuum approximation in the form of two coupled reaction-diffusion equations, which exhibit travelling wave solutions whose speed of invasion depends on the model parameters. We propose a simple analytical method to predict progression rate from the cell-specific parameters and demonstrate that optimal glioblastoma growth depends on a non-trivial trade-off between the phenotypic switching rates. By linking cellular properties to an in vivo outcome, the model should be applicable to designing relevant cell screens for glioblastoma and cytometry-based patient prognostics.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
/
Glioblastoma
/
Modelos Biológicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article