Eph receptors and ephrin ligands: important players in angiogenesis and tumor angiogenesis

Abstract

Eph receptors and their ephrin ligands were identified in the late 1980's. Subsequently, they were linked to different physiological and pathophysiological processes like embryonic development, angiogenesis, and tumorigenesis. In this regard, recent work focused on the distribution and effects of Eph receptors and ephrins on tumor cells and tumor microenvironment. The purpose of this review is to outline the role of these molecules in physiological angiogenesis and pathophysiological tumor angiogenesis. Furthermore, novel therapeutical approaches are discussed as Eph receptors and ephrins represent attractive targets for antiangiogenic therapy.

Figure 1

Structure of Eph receptors and ephrin ligands. PDZ: Postsynaptic density 95-Discs large-Zonula occludentes-1-protein, GPI: glycosylphosphatidylinositol.

Figure 2

Major interactions of Eph receptors and ephrin ligands.

Figure 3

Potential target sites for Eph receptor/ephrin-associated antiangiogenic therapy. The illustrated strategies for intracellular inhibition of forward signaling via kinase inhibitors and gene silencing, respectively, also could be applied for reverse signaling. PDZ: Post synaptic density 95-Discs large-Zonula occludentes-1-protein, siRNA: small interfering RNA, AS-ODN: antisense oligodeoxynucleotides, Rho: Rho-GTPase Src: Src kinase, Akt: Akt kinase, MAPK: mitogen-activated protein kinase.