Abstract

Metastasis on a Chip: Effects of Intravascular and Transendothelial Flow

Roger Kamm, Cecil and Ida Green Distinguished Professor of Biological and Mechanical Engineering, Massachusetts Institute of Technology (MIT)

Circulating tumor cells (CTC) experience a hostile environment due circulating immune cells and the forces combined with vascular shear stress and pressure gradients.  In this study, we examine flow effects on CTC adhesion, migration and transendothelial migration.  Many CTCs fail to survive the voyage from the primary tumor to the metastatic site, and die before they can initiate a new tumor.  Others not only survive, but enter into the tissue where some fraction proliferate and spread.  We studied the effects of vascular flows, both intravascular (IVF) and transendothelial (TEF) on tumor cell adhesion, migration and transendothelial migration with the goal of better understanding how flow either promotes or impedes metastasis.  Our results show that CTCs migrate or are dragged in the direction of flow prior to trans-endothelial migration.  We also observe enhanced potential for TEM due to IVF.  TEF, on the other hand, has little effect on either migration along the luminal surface of the endothelium or the propensity to undergo trans-endothelial migration, but hastens the process once initiated.  Moreover, TEF increased the migration speed of tumor cells post-extravasation, and caused the cells to remain close to the outer endothelial surface. In summary, both types of flow tend to promote a pro-metastatic phenotype.