Abstract
Spatio-temporal models have long been used to describe biological systems of cancer but it has not been until very recently that increased attention has been paid to structural dynamics of the interaction between cancer populations and the molecular mechanisms associated with local invasion. One system that is of particular interest is that of the urokinase plasminogen activator (uPA) wherein uPA binds uPA receptors (uPARs) on the cancer cell surface, allowing plasminogen to be cleaved into plasmin, which degrade the extra cellular matrix (ECM) and this way leads to enhanced cancer cell migration. In this paper we develop a novel numerical approach and associated analysis for spatio-structuro-temporal modelling of the uPA system for up to twospatial and two-structural dimensions. This is accompanied by analytical exploration of the numerical techniques used in simulating this system, with special consideration being given to the proof of stability within numerical regimes encapsulating a central differences approach to approximating numerical gradients. The stability analysis performed here reveals instabilities induced by the coupling of the structural binding and proliferative processes. The numerical results expounds how the uPA system aids the tumour in invading the local stroma, whilst the inhibitor to this system may impede this behaviour and encourage a more sporadic pattern of invasion.
Original language | English |
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Pages (from-to) | 701-737 |
Number of pages | 37 |
Journal | Bulletin of Mathematical Biology |
Volume | 80 |
Issue number | 4 |
Early online date | 2 Mar 2018 |
DOIs | |
Publication status | Published - 1 Apr 2018 |
Keywords
- Cancer invasion
- Computational modelling
- Structured cell population dynamics
ASJC Scopus subject areas
- General Neuroscience
- Immunology
- General Mathematics
- General Biochemistry,Genetics and Molecular Biology
- General Environmental Science
- Pharmacology
- General Agricultural and Biological Sciences
- Computational Theory and Mathematics