论文标题
物理限制和细胞接近增加细胞迁移率和侵入性:通过柔性通道的癌细胞侵袭的数学模型
Physical Confinement and Cell Proximity Increase Cell Migration Rates and Invasiveness: A Mathematical Model of Cancer Cell Invasion through Flexible Channels
论文作者
论文摘要
不同身体部位之间的癌细胞迁移是癌症转移的驱动力,这是患者死亡率的主要原因。癌细胞的迁移通常是通过穿透局部僵硬但柔性组织的狭窄空腔而进行的。在我们以前的工作中,我们开发了一个在侵袭过程中的细胞几何发展模型,我们在此扩展了该模型,以调查仅机械相互作用的领导者和追随者(癌症)细胞是否可以通过狭窄的微通道和空腔中的顺序迁移中受益。 我们考虑了两种细胞的病例,它们依次通过柔性通道迁移:领导者和追随者细胞紧密相邻或远处。我们使用Wilcoxon的签名级测试对从蒙特卡洛模拟收集的数据进行了结论,我们得出结论,当模型的追随者细胞的建模转移速度明显大于细胞远处的领导者细胞,即在领导者完成交叉点后移民的自行车细胞。此外,似乎在通道的宽度方面存在最佳,使细胞移动最快。另一方面,在紧密相邻的单元格的情况下,有效地执行集体迁移,由于追随者细胞将其推动,因此Leader Cell的移动速度更快。这项工作表明,细胞之间的机械相互作用可以增加癌细胞的净迁移速度,从而增加侵入性。换句话说,癌细胞之间的相互作用可以加速转移性侵袭。
Cancer cell migration between different body parts is the driving force behind cancer metastasis, which is the main cause of mortality of patients. Migration of cancer cells often proceeds by penetration through narrow cavities in locally stiff, yet flexible tissues. In our previous work, we developed a model for cell geometry evolution during invasion, which we extend here to investigate whether leader and follower (cancer) cells that only interact mechanically can benefit from sequential transmigration through narrow micro-channels and cavities. We consider two cases of cells sequentially migrating through a flexible channel: leader and follower cells being closely adjacent or distant. Using Wilcoxon's signed-rank test on the data collected from Monte Carlo simulations, we conclude that the modelled transmigration speed for the follower cell is significantly larger than for the leader cell when cells are distant, i.e. follower cells transmigrate after the leader has completed the crossing. Furthermore, it appears that there exists an optimum with respect to the width of the channel such that cell moves fastest. On the other hand, in the case of closely adjacent cells, effectively performing collective migration, the leader cell moves $12\%$ faster since the follower cell pushes it. This work shows that mechanical interactions between cells can increase the net transmigration speed of cancer cells, resulting in increased invasiveness. In other words, interaction between cancer cells can accelerate metastatic invasion.