Computational Approaches and Analysis for a Spatio-Structural-Temporal Invasive Carcinoma Model

Arran Hodgkinson, Mark A. J. Chaplain, Pia Domschke, Dumitru Trucu (Lead / Corresponding author)

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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 languageEnglish
Pages (from-to)701-737
Number of pages37
JournalBulletin of Mathematical Biology
Volume80
Issue number4
Early online date2 Mar 2018
DOIs
Publication statusPublished - 1 Apr 2018

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Keywords

  • Cancer invasion
  • Computational modelling
  • Structured cell population dynamics

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