2019/07/02 by Robyn Shuttleworth, Shuttleworth, Robyn, Dumitru Trucu +1
Biochemistry, Genetics and Molecular Biology · Mathematics · #Cellular Mechanics and Interactions #Dynamical Systems (math.DS) #FOS: Biological sciences #FOS: Mathematics #Mathematical Biology Tumor Growth #Microtubule and mitosis dynamics #Tissues and Organs (q-bio.TO)
paper · pdf · doi:10.48550/arxiv.1907.01575
openalex publication_date 2019/07/02 · openalex created_date 2022/07/28 · openalex updated_date 2026/07/28
Local cancer invasion of tissue is a complex, multiscale process which plays\nan essential role in tumour progression. Occurring over many different temporal\nand spatial scales, the first stage of invasion is the secretion of matrix\ndegrading enzymes (MDEs) by the cancer cells that consequently degrade the\nsurrounding extracellular matrix (ECM). This process is vital for creating\nspace in which the cancer cells can progress and it is driven by the activities\nof specific matrix metalloproteinases (MMPs). In this paper, we consider the\nkey role of two MMPs by developing further the novel two-part multiscale model\nintroduced in [33] to better relate at micro-scale the two micro-scale\nactivities that were considered there, namely, the micro-dynamics concerning\nthe continuous rearrangement of the naturally oriented ECM fibres within the\nbulk of the tumour and MDEs proteolytic micro-dynamics that take place in an\nappropriate cell-scale neighbourhood of the tumour boundary. Focussing\nprimarily on the activities of the membrane-tethered MT1-MMP and the soluble\nMMP-2 with the fibrous ECM phase, in this work we investigate the MT1-MMP/MMP-2\ncascade and its overall effect on tumour progression. To that end, we will\npropose a new multiscale modelling framework by considering the degradation of\nthe ECM fibres not only to take place at macro-scale in the bulk of the tumour\nbut also explicitly in the micro-scale neighbourhood of the tumour interface as\na consequence of the interactions with molecular fluxes of MDEs that exercise\ntheir spatial dynamics at the invasive edge of the tumour.\n