Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago de Compostela (IDIS), University Hospital of Santiago de Compostela (SERGAS), Trav. Choupana s/n, 15706, Santiago de Compostela, Spain.
Institute CRETUS, Group of Nonlinear Physics, Department of Physics, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain.
Sci Rep. 2021 Dec 1;11(1):23231. doi: 10.1038/s41598-021-02482-x.
Homing of circulating tumour cells (CTC) at distant sites represents a critical event in metastasis dissemination. In addition to physical entrapment, probably responsible of the majority of the homing events, the vascular system provides with geometrical factors that govern the flow biomechanics and impact on the fate of the CTC. Here we mathematically explored the distribution of velocities and the corresponding streamlines at the bifurcations of large blood vessel and characterized an area of low-velocity at the carina of bifurcation that favours the residence of CTC. In addition to this fluid physics effect, the adhesive capabilities of the CTC provide with a biological competitive advantage resulting in a marginal but systematic arrest as evidenced by dynamic in vitro recirculation in Y-microchannels and by perfusion in in vivo mice models. Our results also demonstrate that viscosity, as a main determinant of the Reynolds number that define flow biomechanics, may be modulated to limit or impair CTC accumulation at the bifurcation of blood vessels, in agreement with the apparent positive effect observed in the clinical setting by anticoagulants in advanced oncology disease.
循环肿瘤细胞 (CTC) 在远处部位的归巢是转移扩散的一个关键事件。除了可能导致大多数归巢事件的物理截留外，血管系统还提供了控制血流生物力学并影响 CTC 命运的几何因素。在这里，我们从数学上探讨了大血管分叉处的速度分布和相应的流线，并在分叉的嵴处描述了一个低速度区域，有利于 CTC 的停留。除了这种流体物理效应外，CTC 的黏附能力提供了一种生物学竞争优势，导致 CTC 出现轻微但系统的停滞，这在 Y 型微通道中的体外动态再循环和体内小鼠模型中的灌注中得到了证实。我们的研究结果还表明，作为决定血流生物力学的雷诺数主要决定因素的粘度，可通过调制来限制或损害 CTC 在血管分叉处的积累，这与在晚期肿瘤疾病中抗凝剂在临床环境中观察到的明显积极效果一致。
