Circulating
prostate cancer (PCa) cells preferentially roll and adhere on bone marrow vascular endothelial cells, where abundant
E-selectin and
stromal cell-derived factor 1 (SDF-1) are expressed, subsequently initiating a cascade of activation events that eventually lead to the development of
metastases. To elucidate the roles of circulating PCa cells' rolling and adhesion behaviors in
cancer metastases, we applied a dynamic cylindrical flow-based microchannel device that is coated with
E-selectin and SDF-1, mimicking capillary endothelium. Using this device we captured a small fraction of rolling PCa cells. These rolling cells display higher static adhesion ability, more aggressive
cancer phenotypes and stem-like properties. Importantly, mice received rolling PCa cells, but not floating PCa cells, developed
cancer metastases. Genes coding for
E-selectin ligands and genes associated with cancer stem cells and
metastasis were elevated in rolling PCa cells. Knock down of
E-selectin ligand 1(ESL-1), significantly impaired PCa cells' rolling capacity and reduced
cancer aggressiveness. Moreover, ESL-1 activates RAS and MAP
kinase signal cascade, consequently inducing the downstream targets. In summary, circulating PCa cells' rolling capacity contributes to PCa
metastasis, and that is in part controlled by ESL-1.