Evidence to show that the Eph/ephrin system is involved in inflammation induced by
infection, injury, inflammatory diseases, and atherosclerosis has been increased. Although the roles
of the Eph/ephrin system in both neural and vascular development as well as cell motility are well
documented, its involvement in inflammatory processes has not yet been elucidated in detail.
Moreover, the soluble form of artificially oligomerized or dimerized Fc-fused ephrin-A1 has been
widely used in in vitro and/or in vivo studies to activate the EphA receptors, whereas its physiological
functions as a membrane-anchored protein remain largely unknown. Recent studies using clinical
samples reported that the overexpression of Ephs and ephrins in some tumors such as hepatocellular carcinoma positively
correlated with both malignancy of tumors and the poor prognosis of cancer patients. However, the molecular mechanisms
underlying malignancy of tumors are not fully understood. The author herein summarizes the molecular mechanisms of
the Eph/ephrin system involved in the immune system and inflammatory processes. Especially, the author focuses on
inflammation-induced physiological changes in vascular endothelial cells leading to vascular hyper-permeability and
described them in this review. The author also introduces those that contribute to ephrin-A1-mediated lung metastasis.