Department of Bioengineering, Lehigh University, Bethlehem, Pennsylvania 18015, United States.
Department of Mechanical Engineering and Mechanics, Lehigh University, Bethlehem, Pennsylvania 18015, United States.
Anal Chem. 2022 Sep 6;94(35):12159-12166. doi: 10.1021/acs.analchem.2c02556. Epub 2022 Aug 23.
Cancer metastasis counts for 90% of cancer fatalities, and its development process is still a mystery. The dynamic process of tumor metastatic transport in the blood vessel is not well understood, in which some biomechanical factors, such as shear stress and various flow patterns, may have significant impacts. Here, we report a microfluidic vessel-on-a-chip platform for recapitulating several key metastatic steps of tumor cells in blood vessels on the same chip, including intravasation, circulating tumor cell (CTC) vascular adhesion, and extravasation. Due to its excellent adaptability, our system can reproduce various microenvironments to investigate the specific interactions between CTCs and blood vessels. On the basis of this platform, effects of important biomechanical factors on CTC adhesion such as vascular surface properties and vessel geometry-dependent hemodynamics were specifically inspected. We demonstrated that CTC adhesion is more likely to occur under certain mechano-physiological situations, such as vessels with vascular glycocalyx (VGCX) shedding and hemodynamic disturbances. Finally, computational models of both the fluidic dynamics in vessels and CTC adhesion were established based on the confocal scanned 3D images. The modeling results are believed to provide insights into exploring tumor metastasis progression and inspire new ideas for anticancer therapy development.
癌症转移导致了 90%的癌症死亡，其发展过程仍然是一个谜。肿瘤在血管中转移的动态过程还没有被很好地理解，其中一些生物力学因素，如切应力和各种流动模式，可能会产生重大影响。在这里，我们报告了一种微流控血管芯片平台，用于在同一芯片上再现肿瘤细胞在血管中几个关键的转移步骤，包括血管内渗、循环肿瘤细胞（CTC）血管黏附和血管外渗。由于其出色的适应性，我们的系统可以再现各种微环境，以研究 CTC 与血管之间的特定相互作用。在此平台的基础上，特别检查了重要的生物力学因素对 CTC 黏附的影响，如血管表面特性和依赖于血管几何形状的血液动力学。我们证明了 CTC 黏附更有可能在某些力学生理情况下发生，例如血管糖萼（VGCX）脱落和血液动力学紊乱。最后，基于共聚焦扫描的 3D 图像，建立了血管内流场和 CTC 黏附的计算模型。建模结果有助于深入了解肿瘤转移进展，并为抗癌治疗的发展提供新的思路。
