Adaptable Microfluidic Vessel-on-a-Chip Platform for Investigating Tumor Metastatic Transport in Bloodstream.

Abstract

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.