Morley Sinéad T, Walsh Michael T, Newport David T
School of Engineering, Bernal Institute, Faculty of Science and Engineering, University of Limerick, Limerick, Ireland.
Biomicrofluidics. 2017 May 5;11(3):034105. doi: 10.1063/1.4983149. eCollection 2017 May.
The lymphatic system is an extensive vascular network that serves as the primary route for the metastatic spread of breast cancer cells (BCCs). The dynamics by which BCCs travel in the lymphatics to distant sites, and eventually establish metastatic tumors, remain poorly understood. Particle tracking techniques were employed to analyze the behavior of MCF-7 and MDA-MB-231 BCCs which were exposed to lymphatic flow conditions in a 100 m square microchannel. The behavior of the BCCs was compared to rigid particles of various diameters (η = d/H= 0.05-0.32) that have been used to simulate cell flow in lymph. Parabolic velocity profiles were recorded for all particle sizes. All particles were found to lag the fluid velocity, the larger the particle the slower its velocity relative to the local flow (5%-15% velocity lag recorded). A distinct difference between the behavior of BCCs and particles was recorded. The BCCs travelled approximately 40% slower than the undisturbed flow, indicating that morphology and size affects their response to lymphatic flow conditions (1). BCCs adhered together, forming aggregates whose behavior was irregular. At lymphatic flow rates, MCF-7s were distributed uniformly across the channel in comparison to the MDA-MB-231 cells which travelled in the central region (88% of cells found within 0.35 ≤ W ≤ 0.64), indicating that metastatic MDA-MB-231 cells are subjected to a lower range of shear stresses . This suggests that both size and deformability need to be considered when modelling BCC behavior in the lymphatics. This finding will inform the development of lymphatic flow and metastasis models.
淋巴系统是一个广泛的血管网络,是乳腺癌细胞(BCCs)转移扩散的主要途径。BCCs在淋巴管中向远处转移并最终形成转移瘤的动态过程仍知之甚少。采用粒子追踪技术分析了MCF-7和MDA-MB-231 BCCs在100μm方形微通道中暴露于淋巴流条件下的行为。将BCCs的行为与各种直径(η=d/H=0.05-0.32)的刚性粒子进行比较,这些粒子已被用于模拟淋巴中的细胞流动。记录了所有粒径的抛物线速度分布。发现所有粒子的速度都滞后于流体速度,粒子越大,其相对于局部流动的速度越慢(记录到5%-15%的速度滞后)。记录到BCCs和粒子行为之间存在明显差异。BCCs的移动速度比未受干扰的流动速度慢约40%,这表明形态和大小会影响它们对淋巴流条件的反应(1)。BCCs黏附在一起,形成行为不规则的聚集体。在淋巴流速下,与在中央区域移动的MDA-MB-231细胞相比,MCF-7细胞在通道中均匀分布(88%的细胞位于0.35≤W≤0.64范围内),这表明转移性MDA-MB-231细胞受到的剪切应力范围较低。这表明在模拟BCCs在淋巴管中的行为时,需要同时考虑大小和可变形性。这一发现将为淋巴流和转移模型的开发提供参考。