Cell-Scale Degradation of Peritumoural Extracellular Matrix Fibre Network and Its Role Within Tissue-Scale Cancer Invasion

Bull Math Biol. 2020 May 26;82(6):65. doi: 10.1007/s11538-020-00732-z.

Abstract

Local cancer invasion of tissue is a complex, multiscale process which plays an essential role in tumour progression. During the complex interaction between cancer cell population and the extracellular matrix (ECM), of key importance is the role played by both bulk two-scale dynamics of ECM fibres within collective movement of the tumour cells and the multiscale leading edge dynamics driven by proteolytic activity of the matrix-degrading enzymes (MDEs) that are secreted by the cancer cells. As these two multiscale subsystems share and contribute to the same tumour macro-dynamics, in this work we develop further the model introduced in Shuttleworth and Trucu (Bull Math Biol 81:2176-2219, 2019. https://doi.org/10.1007/s11538-019-00598-w) by exploring a new aspect of their interaction that occurs at the cell scale. Specifically, here we will focus on understanding the cell-scale cross talk between the micro-scale parts of these two multiscale subsystems which get to interact directly in the peritumoural region, with immediate consequences both for MDE micro-dynamics occurring at the leading edge of the tumour and for the cell-scale rearrangement of the naturally oriented ECM fibres in the peritumoural region, ultimately influencing the way tumour progresses in the surrounding tissue. To that end, we will propose a new modelling that captures the ECM fibres degradation not only at macro-scale in the bulk of the tumour but also explicitly in the micro-scale neighbourhood of the tumour interface as a consequence of the interactions with molecular fluxes of MDEs that exercise their spatial dynamics at the invasive edge of the tumour.

Keywords: Cancer invasion; ECM fibre dynamics; Multiscale modelling.

MeSH terms

  • Collagen Type I / metabolism
  • Computational Biology
  • Computer Simulation
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology*
  • Extracellular Matrix Proteins / metabolism
  • Humans
  • Mathematical Concepts
  • Matrix Metalloproteinase 14 / metabolism
  • Matrix Metalloproteinase 2 / metabolism
  • Models, Biological*
  • Neoplasm Invasiveness / pathology*
  • Neoplasm Invasiveness / physiopathology
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Peptide Hydrolases / metabolism
  • Proteolysis
  • Tumor Microenvironment / physiology

Substances

  • Collagen Type I
  • Extracellular Matrix Proteins
  • Peptide Hydrolases
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP14 protein, human
  • Matrix Metalloproteinase 14