Chapter category: Neuroscience
The Role of Neuropilin in Vascular and Tumor Biology
Neuropilin: From Nervous System
to Vascular and Tumor Biology
Edited by: Dominique BagnardISBN: 0-306-47416-6
» Get more information about this book at landesbioscience.com «
Chapter authors:
Michael Klagsbrun, Seiji Takashima and Roni Mamluk
Neuropilin1 (NRP1) and NRP2 are related transmembrane receptors that function as mediators of neuronal guidance and angiogenesis. NRPs bind members of the class 3 semaphorin family, regulators of neuronal guidance, and of the vascular endothelial growth factor (VEGF) family of angiogenesis factors. There is substantial evidence that NRPs serve as mediators of developmental and tumor angiogenesis. NRPs are expressed in endothelial cells (EC) and bind VEGF165. NRP1 is a coreceptor for VEGF receptor2 (VEGFR2) that enhances the binding of VEGF165 to VEGFR2 and VEGF165mediated chemotaxis. NRP1 expression is regulated in EC by tumor necrosis factora, the transcription factors dHAND and Ets1, and vascular injury. During avian blood vessel development NRP1 is expressed only in arteries whereas NRP2 is expressed in veins. Transgenic mouse models demonstrate that NRP1 plays a critical role in embryonic vascular development. Overexpression of NRP1 results in the formation of excess capillaries and hemorrhaging. NRP1 knockouts have defects in yolk sac, embryo and neuronal vascularization, and in development of large vessels in the heart. Tumor cells express NRPs and bind VEGF165. NRP1 upregulation is positively correlated with the progression of various tumors. Overexpression of NRP1 in rat tumor cells results in enlarged tumors and substantially enhanced tumor angiogenesis. On the other hand, soluble NRP1 (sNRP1) is an antagonist of tumor angiogenesis. Semaphorin 3A binds to EC and tumor cells. It also inhibits EC motility and capillary sprouting in vitro. VEGF165 and Sema3A are competitive inhibitors for NRP1 mediated functions in EC and neurons. These results suggest that NRP1 is a novel regulator of the vascular system.
Additional chapters from this book:
Neuropilin and Class 3 Semaphorins in Nervous System Regeneration
Fred De Winter, Anthony J.G.D. Holtmaat and Joost Verhaagen
Injury to the mature mammalian central nervous system (CNS) is often accompanied by permanent loss of function of the damaged neural circuits. The failure of injured CNS axons to regenerate...
Neuropilin and its Ligands in Normal Lung and Cancer
Joëlle Roche, Harry Drabkin and Elisabeth Brambilla
Neuropilins (NRPs) are receptors for class 3 Semaphorins and function as co-receptors for Vascular endothelial growth factor isoforms, VEGF165 and VEGF145 and related mol...
The Function of Neuropilin / L1 Complex
V. Castellani
L1, a cell adhesion molecule of the Ig superfamily (IgCAM) plays a critical role in the formation of neuronal networks. This is reflected by the variety of clinical signs associated with the X...
The Interaction of Neuropilin-1 and Neuropilin-2 with Tyrosine-Kinase Receptors or VEGF
Gera Neufeld, Ofra Kessler and Yael Herzog
The Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2) receptors were initially described as receptors for axon guidance factors belonging to the class-3 Semaphorin sub-family. Subsequently, it wa...
The Function of Neuropilin/Plexin Complexes
Andreas W. Püschel
Neuropilins bind the secreted class 3 semaphorins with high affinity but require a member of the plexin family to form receptors that are able to activate downstream signal transduction cascad...
Structural and Functional Relation of Neuropilins
Fumio Nakamura and Yoshio Goshima
Neuropilin is a type I transmembrane protein and the molecular mass is 120 kDa. Two homologues, Neuropilin-1 and -2, are identified. The primary structure of Neuropilin-1 and Neuropilin-2 is w...
Neuropilin-1 in the Immune System
Paul-Henri Romeo, Valérie Lemarchandel and Rafaele Tordjman
The neuropilin-1 (NRP1) and neuropilin-2 (NRP2) receptors can bind the class-3 semaphorin subfamily and the heparin-binding forms of vascular endothelial growth factor (VEGF) and placenta grow...
The Role of Neuropilin in Vascular and Tumor Biology
Michael Klagsbrun, Seiji Takashima and Roni Mamluk
Neuropilin1 (NRP1) and NRP2 are related transmembrane receptors that function as mediators of neuronal guidance and angiogenesis. NRPs bind members of the class 3 semaphorin family, regulators...
Neuropilins as Semaphorin Receptors: In vivo Functions in Neuronal Cell
Anil Bagri and Marc Tessier-Lavigne
After the initial discovery of neuropilin-1 as an epitope on axons recognized by a monoclonal antibody, neuropilins were rediscovered in the search for receptors mediating the repulsive action...
From the Discovery of Neuropilin to the Determination of its Adhesion Sites
Hajime Fujisawa
Neuropilin (NRP) and plexin (Plex) that are now known to be semaphorin receptors were initially identified as antigens for monoclonal antibodies (MAbs) that bound to particular neuropiles and ...
