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

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.