Fibrinogen and fibrin differentially regulate the local hydrodynamic environment in neutrophil–tumor cell–endothelial cell adhesion system

Abstract

As cancer is one of the major fatal diseases for human beings worldwide, the metastasis of tumor cells (TCs) from a blood vessel to an adjacent organ has become a focus of research. A tumor metastasis theory named the “two-step theory” pointed out that polymorphnuclear neutrophils (PMNs) could facilitate TC adhesion on an endothelial monolayer under flow, which was regulated by shear flow and promoted by fibrinogen and fibrin. In order to further understand the role of hydrodynamics played in the “two-step theory”, we improved our side-view micro-particle imaging velocimetry (PIV) system and successfully measured the flow velocity profiles around adherent PMNs and TCs on an endothelial monolayer in the presence of soluble fibrinogen or fibrin under shear flow. Combined with a computational fluid dynamics simulation, we found that: (1) soluble fibrinogen and fibrin influenced the variations of relative shear rates above an adhered PMN and an adherent TC at different PMN-to-TC position states; (2) compared with soluble fibrinogen, soluble fibrin made the curves of relative shear rates above an adherent cell flatter. Soluble fibrin might increase the collision frequency and affect the contact time and contact area between PMNs, TCs, and endothelium cells, resulting in the enhancement of TC adhesion and retention on an endothelial monolayer.