A review on the role of different ephrins in glioma.

Gliomas, tumors of glial cells, are the most common malignant tumors of the brain. Ephrins are protein ligands that act through tyrosine kinases receptor family, Eph receptors. In glioma, an inverse relationship has been identified between ephrin A1 ligand and EphA2 receptors i.e. there has been a decrease in the expression of ephrin A1 and increase in the expression of EphA2. The forced expression of ephrin A1 decreases the proliferation of glioma by internalizing the EphA2 receptors. The ligand (ephrin A1)-independent effects of EphA2 receptors are oncogenic in nature, while the binding of EphA2 with ephrin A1 decreases the glioma proliferation. An increase in EphA4 may be important in enhancing cellular proliferation and migration of glioblastoma through FGFR-MAPK-Akt signaling pathway, while a decrease in the expression of EphA5 may be crucial in increasing the cellular proliferation and thus, ephrin A5 acts as a tumor suppressor in glioma by negatively regulating the expression of EGFR. The higher expression levels of EphB2 and its ligand, ephrin B1 may decrease the cell adhesion and increase the invasion capacity of glioma through HIF-2α-EphB2-paxillin signalling. There is also a key role of ephrin B2 and EphB2 in promoting migration, invasion and conferring resistance to glioma cell. Ephrin B2 contributes in the pathogenesis of glioma by promoting angiogenesis through VEGF-A. An increase in ephrin B3 may also be important in the increasing tumorigenicity of glioma. The present review describes the role of different ephrins in the pathogenesis of glioma.