Characterization of the Effects of Semaphorin 4D Signaling on Angiogenesis

The semaphorins and plexins comprise a family of cysteine-rich cell surface and secreted proteins originally shown to control nerve growth and the immune response, but that have recently been implicated in a wide variety of developmental and pathological processes that are influenced by cell adhesion and migration. Along those lines, our group and others have found that Semaphorin 4D (SEMA4D) plays an important role in angiogenesis by promoting chemotaxis of endothelial cells, which express its receptor, Plexin-B1. Indeed, some neoplasms produce SEMA4D along with other pro-angiogenic proteins for the purpose of enhancing blood vessel growth into a developing neoplasm. Here we describe the application of in vitro migration and tubulogenesis assays and the directed in vivo angiogenesis assay (DIVAA) in the measurement of the angiogenic potential of cell-derived and soluble SEMA4D.