  Vascular adhesion of circulating tumor cells (CTCs) is a key step in cancer
spreading. If inflammation is recognized to favor the formation of vascular
metastatic niches, little is known about the contribution of blood rheology to
CTC deposition. Herein, a microfluidic chip, covered by a confluent monolayer
of endothelial cells, is used for analyzing the adhesion and rolling of
colorectal (HCT 15) and breast (MDA MB 231) cancer cells under different
biophysical conditions. These include the analysis of cell transport in a
physiological solution and whole blood; over a healthy and a TNF alpha inflamed
endothelium; with a flow rate of 50 and 100 nL/min. Upon stimulation of the
endothelial monolayer with TNF alpha (25 ng/mL), CTC adhesion increases by 2 to
4 times whilst cell rolling velocity only slightly reduces. Notably, whole
blood also enhances cancer cell deposition by 2 to 3 times, but only on the
unstimulated vasculature. For all tested conditions, no statistically
significant difference is observed between the two cancer cell types. Finally,
a computational model for CTC transport demonstrates that a rigid cell
approximation reasonably predicts rolling velocities while cell deformability
is needed to model adhesion. These results would suggest that, within
microvascular networks, blood rheology and inflammation contribute similarly to
CTC deposition thereby facilitating the formation of metastatic niches along
the entire network, including the healthy endothelium. In microfluidic based
assays, neglecting blood rheology would significantly underestimate the
metastatic potential of cancer cells.
