E-selectin was first discovered as an transmembrane receptor induced in endothelial cells upon inflammatory stimulation which mediated adhesion of monocytic or HL60 leukemic cells. This led to the hypothesis that cancer cells secreted inflammatory cytokines such as IL-1β or TNFα to induce E-selectin at distant metastatic sites. This induction would enable circulating tumor cells to arrest at stimulated sites, roll along activated endothelium, extravasate, and form metastases. Studies since have showed that E-selectin binding to colon cancer cells correlates with increasing metastatic potential, and that cancer cells of multiple tumor types bind E-selectin using glycoprotein or glycolipid ligands normally expressed on immune cells. Studies have further described a mechanistic cascade wherein cancer cells first bind E-selectin at shear flow rates: E-selectin binding results in a velcro-like interaction allowing the cancer cells to engage higher affinity integrin binding that eventually results in a tight binding between tumor cells and the activated endothelium.