Journal ArticleDOI
Class 3 semaphorins control vascular morphogenesis by inhibiting integrin function
Guido Serini,Donatella Valdembri,Sara Zanivan,Giulia Morterra,Constanze Burkhardt,Francesca Caccavari,Luca Zammataro,Luca Primo,Luca Tamagnone,Malcolm Logan,Marc Tessier-Lavigne,Masahiko Taniguchi,Andreas W. Püschel,Federico Bussolino +13 more
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TLDR
During angiogenesis endothelial SEMA3 proteins endow the vascular system with the plasticity required for its reshaping by controlling integrin function.Abstract:
The motility and morphogenesis of endothelial cells is controlled by spatio-temporally regulated activation of integrin adhesion receptors, and integrin activation is stimulated by major determinants of vascular remodelling. In order for endothelial cells to be responsive to changes in activator gradients, the adhesiveness of these cells to the extracellular matrix must be dynamic, and negative regulators of integrins could be required. Here we show that during vascular development and experimental angiogenesis, endothelial cells generate autocrine chemorepulsive signals of class 3 semaphorins (SEMA3 proteins) that localize at nascent adhesive sites in spreading endothelial cells. Disrupting endogenous SEMA3 function in endothelial cells stimulates integrin-mediated adhesion and migration to extracellular matrices, whereas exogenous SEMA3 proteins antagonize integrin activation. Misexpression of dominant negative SEMA3 receptors in chick embryo endothelial cells locks integrins in an active conformation, and severely impairs vascular remodelling. Sema3a null mice show vascular defects as well. Thus during angiogenesis endothelial SEMA3 proteins endow the vascular system with the plasticity required for its reshaping by controlling integrin function.read more
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Common mechanisms of nerve and blood vessel wiring
TL;DR: The discovery of key axon guidance molecules over the past decade has shown that axons are guided to their targets by finely tuned codes of attractive and repulsive cues, and recent studies reveal that these cues also help blood vessels to navigate to their target.
Patent
Delivery system attachment
Guobao Wei,Keyvan Behnam,Nanette Forsyth,John Winterbottom,James Beisser,Todd M. Boyce,Mohamed Attawia,Cristy Richards,Lawrence A. Shimp +8 more
TL;DR: In this paper, a covering for delivering a substance or material to a surgical site is provided, with substance provided therein, may be referred to as a delivery system, and the covering may participate in, control, or otherwise adjust, the release of the substance.
Journal ArticleDOI
Blocking Neuropilin-1 Function Has an Additive Effect with Anti-VEGF to Inhibit Tumor Growth
Qi Pan,Yvan Chanthery,Wei-Ching Liang,Scott Stawicki,Judy Mak,Nisha Rathore,Raymond K. Tong,Joe Kowalski,Sharon Yee,Glenn Pacheco,Sarajane Ross,Zhiyong Cheng,Jennifer Le Couter,Greg Plowman,Franklin Peale,Alexander W. Koch,Yan Wu,Anil Bagri,Marc Tessier-Lavigne,Ryan J. Watts +19 more
TL;DR: It is proposed that blocking NRP1 function inhibits vascular remodeling, rendering vessels more susceptible to anti-VEGF therapy, and generated two monoclonal antibodies that bind to the Sema- and VEGF-binding domains of N RP1.
Journal ArticleDOI
Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins.
Chenghua Gu,Yutaka Yoshida,Jean Livet,Dorothy V. Reimert,Fanny Mann,Janna Merte,Christopher E. Henderson,Thomas M. Jessell,Alex L. Kolodkin,David D. Ginty +9 more
TL;DR: It is found that signaling by semaphorin 3E (Sema3E) and its receptor plexin-D1 controls endothelial cell positioning and the patterning of the developing vasculature in the mouse.
Journal ArticleDOI
Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis
Suphansa Sawamiphak,Sascha Seidel,Clara L. Essmann,George A. Wilkinson,Mara E. Pitulescu,Till Acker,Amparo Acker-Palmer +6 more
TL;DR: It is suggested that blocking ephrin-B2 reverse signalling may be an attractive alternative or combinatorial anti-angiogenic therapy strategy to disrupt VEGFR2 function in tumour angiogenesis.
References
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Journal ArticleDOI
A series of normal stages in the development of the chick embryo
TL;DR: The preparation of a series of normal stages of the chick embryo does not need justification at a time when chick ernbryos are not only widely used in descriptive and experimental embryology but are proving to be increasingly valuable in medical research, as in work on viruses and cancer.
Journal ArticleDOI
Integrins: Bidirectional, Allosteric Signaling Machines
TL;DR: Current structural and cell biological data suggest models for how integrins transmit signals between their extracellular ligand binding adhesion sites and their cytoplasmic domains, which link to the cytoskeleton and to signal transduction pathways.
Journal ArticleDOI
Cell Migration: A Physically Integrated Molecular Process
TL;DR: The authors are grateful for financial support from the National Institutes of Health (grants GM23244 and GM53905), and to very helpful comments on the manuscript from Elliot Elson, Vlodya Gelfand, Paul Matsudaira, Julie Theriot, and Sally Zigmond.
Journal ArticleDOI
Vascular-specific growth factors and blood vessel formation
George D. Yancopoulos,Samuel Davis,Nicholas W. Gale,John S. Rudge,Stanley J. Wiegand,Jocelyn Holash +5 more
TL;DR: New findings in newly discovered vascular growth factors demand re-evaluation of therapeutic efforts aimed at regulating blood vessel growth in ischaemia, cancer and other pathological settings.
Journal ArticleDOI
Requirement of vascular integrin alpha v beta 3 for angiogenesis
TL;DR: The adhesion receptor integrin alpha v beta 3 was identified as a marker of angiogenic vascular tissue in this paper, and it showed a fourfold increase in expression during angiogenesis on the chick chorioallantoic membrane.