Division of Mathematics, University of Dundee, Dundee, DD1 4HN, UK.
Bull Math Biol. 2020 Nov 19;82(12):148. doi: 10.1007/s11538-020-00819-7.
Invasion of the surrounding tissue is one of the recognised hallmarks of cancer (Hanahan and Weinberg in Cell 100: 57-70, 2000. https://doi.org/10.1016/S0092-8674(00)81683-9 ), which is accomplished through a complex heterotypic multiscale dynamics involving tissue-scale random and directed movement of the population of both cancer cells and other accompanying cells (including here, the family of tumour-associated macrophages) as well as the emerging cell-scale activity of both the matrix-degrading enzymes and the rearrangement of the cell-scale constituents of the extracellular matrix (ECM) fibres. The involved processes include not only the presence of cell proliferation and cell adhesion (to other cells and to the extracellular matrix), but also the secretion of matrix-degrading enzymes. This is as a result of cancer cells as well as macrophages, which are one of the most abundant types of immune cells in the tumour micro-environment. In large tumours, these tumour-associated macrophages (TAMs) have a tumour-promoting phenotype, contributing to tumour proliferation and spread. In this paper, we extend a previous multiscale moving-boundary mathematical model for cancer invasion, by considering also the multiscale effects of TAMs, with special focus on the influence that their directional movement exerts on the overall tumour progression. Numerical investigation of this new model shows the importance of the interactions between pro-tumour TAMs and the fibrous ECM, highlighting the impact of the fibres on the spatial structure of solid tumour.
周围组织的侵袭是癌症的公认标志之一（Hanahan 和 Weinberg 在 Cell 100: 57-70, 2000. https://doi.org/10.1016/S0092-8674(00)81683-9），它是通过涉及组织尺度上癌细胞和其他伴随细胞（包括肿瘤相关巨噬细胞家族）的随机和定向运动的复杂异质多尺度动力学来实现的，以及基质降解酶的细胞尺度活性和细胞外基质 (ECM) 纤维的细胞尺度成分的重新排列。所涉及的过程不仅包括细胞增殖和细胞黏附（与其他细胞和细胞外基质）的存在，还包括基质降解酶的分泌。这是由于癌细胞和巨噬细胞，它们是肿瘤微环境中最丰富的免疫细胞类型之一。在大型肿瘤中，这些肿瘤相关巨噬细胞（TAMs）具有促进肿瘤的表型，有助于肿瘤的增殖和扩散。在本文中，我们通过考虑 TAMs 的多尺度效应，扩展了先前用于癌症侵袭的多尺度运动边界数学模型，特别关注它们的定向运动对整体肿瘤进展的影响。对这个新模型的数值研究表明了促肿瘤 TAMs 与纤维 ECM 之间相互作用的重要性，突出了纤维对实体瘤空间结构的影响。
