Semaphorins in Angiogenesis and Tumor Progression

Abstract

The semaphorins were initially described as axon guidance factors, but have recently been implicated in a variety of physiological and developmental functions, including regulation of immune response, angiogenesis, and migration of neural crest cells. The semaphorin family contains more than 30 genes divided into seven subfamilies, all of which are characterized by the presence of a sema domain. The semaphorins transduce their signals by binding to one of the nine receptors belonging to the plexin family, or, in the case of the class 3 semaphorins, by binding to one of the two neuropilin receptors. Additional receptors, which form complexes with these primary semaphorin receptors, are also frequently involved in semaphorin signaling. Recent evidence suggests that some semaphorins can act as antiangiogenic and/or antitumorigenic agents whereas other semaphorins promote tumor progression and/ or angiogenesis. Furthermore, loss of endogenous inhibitory semaphorin expression or function on one hand, and overexpression of protumorigenic semaphorins on the other hand, is associated with the progression of some tumor types.

The Tissue-Reconstructing Ability of Colon CSCs Is Enhanced by FK506 and Suppressed by GSK3 Inhibition

“…In addition to these normal functions of the semaphorins, many semaphorins have been found to have a functional activity associated with tumor progression (21,22). So far, little has been reported about FAM105A, but FAM105A has a conserved protein domain of Rho-GAP (23), that might regulate the Rho G protein.…”

Semaphorin Signaling in Cardiovascular Development

“…Lymphangiogenesis and Tumor Angiogenesis. Semaphorins, plexins, and neuropilins have all been implicated in tumor angiogenesis, a topic that has been the subject of several excellent recent reviews (Ch'ng and Neufeld and Kessler, 2008;Neufeld et al, 2012;Sakurai et al, 2012). Semaphorin ligands expressed by tumor cells and by tumor-associated immune cells can stimulate pro-angiogenic pathways in endothelial cells, and the possibility of developing anti-angiogenic therapies for cancer by targeting these pathways is being actively explored.…”

“…Semaphorins and neuropilin receptors were initially identified as axon guidance molecules in the developing nervous system (He and Tessier-Lavigne, 1997;Luo et al, 1993). Subsequently, semaphorins have been shown to function in a wide range of developmental, physiological, and pathological processes outside of the central nervous system, including lymphocyte activation, neural crest cell migration, vascular endothelial cell motility, bone growth, tumor angiogenesis and progression, lung branching morphogenesis, and cardiovascular development (Corà et al, 2014;Kruger et al, 2005;Neufeld and Kessler, 2008;Neufeld et al, 2012;Roth et al, 2009).…”

Neuropilin-1 mediates myeloid cell chemoattraction and influences retinal neuroimmune crosstalk

“…However, in diabetes and OIR, retinal ganglion neurons, which are in intimate proximity with retinal vessels, generate significant amounts of this cue (20,21). In addition to a role in local MP chemotaxis, SEMA3A also directly affects microvessels (47) and may directly induce endothelial apoptosis and promote cytoskeleton remodeling (47)(48)(49)(50). Specifically in the retina, SEMA3A hinders physiological vascular regeneration in OIR (21) and provokes pathological compromise of barrier function in DR (20).…”