Ramis-Conde Ignacio, Chaplain Mark A J, Anderson Alexander R A, Drasdo Dirk
French National Institute for Research in Computer Science and Control, Le Chesnay, France.
Phys Biol. 2009 Mar 25;6(1):016008. doi: 10.1088/1478-3975/6/1/016008.
Transendothelial migration is a crucial process of the metastatic cascade in which a malignant cell attaches itself to the endothelial layer forming the inner wall of a blood or lymph vessel and creates a gap through which it enters into the bloodstream (or lymphatic system) and then is transported to distant parts of the body. In this process both biological pathways involving cell adhesion molecules such as VE-cadherin and N-cadherin, and the biophysical properties of the cells play an important role. In this paper, we present one of the first mathematical models considering the problem of cancer cell intravasation. We use an individual force-based multi-scale approach which accounts for intra- and inter-cellular protein pathways and for the physical properties of the cells, and a modelling framework which accounts for the biological shape of the vessel. Using our model, we study the influence of different protein pathways in the achievement of transendothelial migration and give quantitative simulation results comparable with real experiments.
跨内皮迁移是转移级联反应中的一个关键过程，在这个过程中，恶性细胞附着在内皮细胞层上，该内皮细胞层构成血管或淋巴管的内壁，并形成一个间隙，通过这个间隙进入血液循环（或淋巴系统），然后被输送到身体的远处部位。在这个过程中，涉及细胞粘附分子（如血管内皮钙粘蛋白和N-钙粘蛋白）的生物途径以及细胞的生物物理特性都起着重要作用。在本文中，我们提出了首批考虑癌细胞血管内渗问题的数学模型之一。我们使用基于个体力的多尺度方法，该方法考虑了细胞内和细胞间的蛋白质途径以及细胞的物理特性，以及一个考虑血管生物学形状的建模框架。利用我们的模型，我们研究了不同蛋白质途径对实现跨内皮迁移的影响，并给出了与实际实验相当的定量模拟结果。
