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黏附对癌症和发育过程中细胞侵袭的影响。

The impact of adhesion on cellular invasion processes in cancer and development.

机构信息

Department of Mathematics and the Maxwell Institute for Mathematical Sciences, School of Mathematical and Computer Sciences, Heriot-Watt University, Edinburgh EH14 4AS, UK.

出版信息

J Theor Biol. 2010 Jun 7;264(3):1057-67. doi: 10.1016/j.jtbi.2010.03.033. Epub 2010 Mar 25.

Abstract

In this paper we consider a simple continuous model to describe cell invasion, incorporating the effects of both cell-cell adhesion and cell-matrix adhesion, along with cell growth and proteolysis by cells of the surrounding extracellular matrix (ECM). We demonstrate that the model is capable of supporting both noninvasive and invasive tumour growth according to the relative strength of cell-cell to cell-matrix adhesion. Specifically, for sufficiently strong cell-matrix adhesion and/or sufficiently weak cell-cell adhesion, degradation of the surrounding ECM accompanied by cell-matrix adhesion pulls the cells into the surrounding ECM. We investigate the criticality of matrix heterogeneity on shaping invasion, demonstrating that a highly heterogeneous ECM can result in a "fingering" of the invasive front, echoing observations in real-life invasion processes ranging from malignant tumour growth to neural crest migration during embryonic development.

摘要

在本文中,我们考虑了一个简单的连续模型来描述细胞入侵,该模型纳入了细胞-细胞黏附以及细胞-基质黏附的影响,同时还纳入了细胞生长和周围细胞外基质 (ECM) 中细胞的蛋白水解作用。我们证明,根据细胞-细胞黏附与细胞-基质黏附的相对强度,该模型能够支持非侵入性和侵入性肿瘤生长。具体而言,对于足够强的细胞-基质黏附以及/或足够弱的细胞-细胞黏附,周围 ECM 的降解伴随着细胞-基质黏附,将细胞拉入周围的 ECM 中。我们研究了基质异质性对塑造入侵的关键性,表明高度异质的 ECM 可导致入侵前沿的“指状”化,这与现实生活中的入侵过程中的观察结果相呼应,这些过程包括从恶性肿瘤生长到胚胎发育期间神经嵴迁移等。

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