E-selectin
It is a variant of the tyrosine kinase FGF glycoreceptor, raising the possibility that its binding to E-selectin is involved in initiating signaling in the bound cells.The local release of cytokines IL-1 and TNF-α by macrophages in the inflamed tissue induces the over-expression of E-selectin on endothelial cells of nearby blood vessels.[23][24] 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.[34][35] This paradox was more recently solved by a trio of studies showing that E-selectin is only constitutively expressed in the bone marrow endothelium[36] where it is thought to perform functions vital to hematopoiesis.[41] In addition, E-selectin may also function to recruit monocytes to primary tumors or lung metastases to promote an inflammatory pro-tumor microenvironment.In cases of elevated blood glucose levels, such as in sepsis, E-selectin expression is higher than normal, resulting in greater microvascular permeability.[44] Study shows the adherence of Porphyromonas gingivalis to human umbilical vein endothelial cells increases with the induction of E-selectin expression by TNF-α.These results suggest that the interaction between host E-selectin and pathogen Pgm6/7 mediates P. gingivalis adherence to endothelial cells and may trigger vascular inflammation.[45] The immunohistochemical expressions of E-selectin and PECAM-1 were significantly increased at intima in vulnerable plaques of acute coronary syndrome (ACS) group, especially in neovascular endothelial cells, and positively correlated with inflammatory cell density, suggesting that PECAM-1 and E-selectin might play an important role in inflammatory reaction and development of vulnerable plaque.In endothelial cells, various cell-adhesion molecules including E-selectin, are shown to be upregulated upon exposure to nicotine, the addictive component of tobacco smoke.