Multiscale modelling of cancer invasion

: the role of dynamic fibre redistribution and matrix-degrading enzymes in tumour progression

  • Robyn Shuttleworth

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

Recognised as one of the hallmarks of cancer, cancer invasion is a complex process involving the secretion of matrix-degrading enzymes that have the ability to degrade the surrounding extracellular matrix (ECM). Combined with cell proliferation and migration, and changes in cell-cell and cell-matrix adhesion, the tumour is able to spread into the surrounding tissue. The ECM constituents are favourably explored by the cancer cells during invasion, and in this context, of particular importance is the special contribution of ECM fibrous proteins components, such as collagen and fibronectin, which play an important part in cell proliferation and migration.

In this thesis we consider the two-scale dynamic cross-talk between the cancer cell population and a two-component ECM in the context of the proteolytic dynamics of matrix-degrading enzymes at the leading edge of a growing malignant tumour. We incorporate the two-scale dynamics of cells-ECM interactions by exploring key inter- linked tissue-scale and cell-scale aspects contributing directly both to cell-adhesion and to the dynamic rearrangement and restructuring of the ECM fibres within the growing tumour. Finally, this bulk two-scale activity is embedded within a global multiscale moving boundary approach that also crucially accounts for an emerging multiscale dynamics of the matrix degrading enzyme proteolytic processes at the in- vasive edge of the tumour, which lead to peritumoural ECM degradation and results in changes of the tumour morphology and further cancer spread.
Date of Award2019
LanguageEnglish
Awarding Institution
  • University of Dundee
SupervisorDumitru Trucu (Supervisor) & Ping Lin (Supervisor)

Cite this

Multiscale modelling of cancer invasion: the role of dynamic fibre redistribution and matrix-degrading enzymes in tumour progression
Shuttleworth, R. (Author). 2019

Student thesis: Doctoral ThesisDoctor of Philosophy