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.

中文翻译：

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肿瘤周围细胞外基质纤维网络的细胞级降解及其在组织级癌症侵袭中的作用

组织的局部癌症侵袭是一个复杂的、多尺度的过程，在肿瘤进展中起着至关重要的作用。在癌细胞群与细胞外基质 (ECM) 之间复杂的相互作用过程中，至关重要的是 ECM 纤维在肿瘤细胞集体运动中的大量两尺度动力学和由蛋白水解活动驱动的多尺度前沿动力学所发挥的作用由癌细胞分泌的基质降解酶 (MDE)。由于这两个多尺度子系统共享并促成相同的肿瘤宏观动力学，在这项工作中，我们进一步开发了 Shuttleworth 和 Trucu 中引入的模型（Bull Math Biol 81:2176–2219, 2019. https://doi.org/10.1007 /s11538-019-00598-w ）通过探索它们在细胞尺度上发生的相互作用的新方面。具体来说，在这里，我们将重点了解这两个多尺度子系统的微尺度部分之间的细胞尺度串扰，它们直接在肿瘤周围区域相互作用，对发生在肿瘤前沿的 MDE 微动力学产生直接影响以及肿瘤周围区域自然定向的 ECM 纤维的细胞级重排，最终影响肿瘤在周围组织中的进展方式。为此，我们将提出一个新的模型，它不仅在肿瘤的宏观尺度上捕获 ECM 纤维的降解，而且在肿瘤界面的微尺度邻域中也明确地捕获了与分子通量相互作用的结果的 MDE 在肿瘤的侵入边缘行使空间动力学。