Figure 3.

Neutrophils facilitate CTCs extravasation. E/P-selectin on the endothelial cell mediates the initial attachment and rolling of neutrophils along the endothelial surface. Then neutrophils capture tumor cells via LFA-1 and ICAM-1 interactions. LFA-1 on neutrophils also bind to ICAM-1 on the endothelial cells to arrest and activate neutrophils. After arrest, neutrophils within clusters are highly migratory mediated by neutrophils self-secreted IL-8 and tumor-derived CXCL-1. On the other hand, tumor cell secreted IL-8 increases Mac-1 expression on neutrophils to promote their binding to ICAM-1 on endothelial cells, and also prolong interaction with CTCs via Mac-1-mediated interactions with ICAM-1-expressing CTCs. Neutrophils can also facilitate CTCs adhesion to endothelium, which is dependent on selectin ligands containing sialyl-Lewis x (sLex) moieties on the surface of the tumor cells and E-selectin on endothelial cells. Together, neutrophils increase the extravasation potential of nearby entrapped tumor cells through disruption of the endothelial barrier.