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Blood, 1 November 2006, Vol. 108, No. 9, pp. 2914-2922. Prepublished online as a Blood First Edition Paper on July 13, 2006; DOI 10.1182/blood-2006-05-023341. This Article Full Text (PDF) Supplemental Videos All Versions of this Article: blood-2006-05-023341v1 108/9/2914    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Salvucci, O. Articles by Tosato, G. Search for Related Content PubMed PubMed Citation Articles by Salvucci, O. Articles by Tosato, G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 23, 2005 Accepted June 27, 2006 EphB2 and EphB4 receptors forward signaling promotes SDF- 1-induced endothelial cell chemotaxis and branching remodeling Ombretta Salvucci, Maria De La Luz Sierra, Jose A Martina, Peter J McCormick, and Giovanna Tosato* Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD Laboratory of Cell Biology, National Heart, Lung and Blood Institute, NIH, Bethesda, MD, USA * Corresponding author; email: tosatog{at}mail.nih.gov. The complex molecular mechanisms that drive endothelial cell movement and formation of new vessels are poorly understood and require further investigation. Eph receptors tyrosine kinases and their membrane-anchored ephrin ligands regulate cell movements mostly by cell-to- cell contact, whereas the G-protein-coupled receptor CXCR4 and its unique SDF-1 chemokine ligand regulate cell movement mostly through soluble gradients. Here, by using biochemical and functional approaches, we investigated how ephrinB and SDF-1 orchestrate endothelial cell movement and morphogenesis into capillary-like structures. We describe that in primary human endothelial cells endogenous EphB2 and EphB4 signaling is required for the formation of extracellular matrix-dependent capillary-like structures. We further demonstrate that EphB2 and EphB4 activation enhances SDF- 1-induced signaling and chemotaxis that are also required for extracellular matrix-dependent endothelial cell clustering. These results support a model in which SDF-1 gradients first promote endothelial cell clustering, and EphB2 and EphB4 critically contribute to subsequent cell movement and alignment into cord-like structures. This study reveals a requirement for endogenous Eph signaling in endothelial cell morphogenic processes, uncovers a novel link between EphB forward signaling and SDF-1-induced signaling, and demonstrates a mechanism for cooperative regulation of endothelial cell movement. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Arthur, S. Koblar, S. Shi, and S. Gronthos Eph/ephrinB Mediate Dental Pulp Stem Cell Mobilization and Function Journal of Dental Research, September 1, 2009; 88(9): 829 - 834. [Abstract] [Full Text] [PDF] A. Pennisi, W. Ling, X. Li, S. Khan, J. D. Shaughnessy Jr, B. Barlogie, and S. Yaccoby The ephrinB2/EphB4 axis is dysregulated in osteoprogenitors from myeloma patients and its activation affects myeloma bone disease and tumor growth Blood, August 27, 2009; 114(9): 1803 - 1812. [Abstract] [Full Text] [PDF] O. Salvucci, D. Maric, M. Economopoulou, S. Sakakibara, S. Merlin, A. Follenzi, and G. Tosato EphrinB reverse signaling contributes to endothelial and mural cell assembly into vascular structures Blood, August 20, 2009; 114(8): 1707 - 1716. [Abstract] [Full Text] [PDF] B. Annamalai, X. Liu, U. Gopal, and J. S. Isaacs Hsp90 Is an Essential Regulator of EphA2 Receptor Stability and Signaling: Implications for Cancer Cell Migration and Metastasis Mol. Cancer Res., July 1, 2009; 7(7): 1021 - 1032. [Abstract] [Full Text] [PDF] C. Urbich, L. Rossig, D. Kaluza, M. Potente, J.-N. Boeckel, A. Knau, F. Diehl, J.-G. Geng, W.-K. Hofmann, A. M. Zeiher, et al. HDAC5 is a repressor of angiogenesis and determines the angiogenic gene expression pattern of endothelial cells Blood, May 28, 2009; 113(22): 5669 - 5679. [Abstract] [Full Text] [PDF] E. J. Yavrouian, U. K. Sinha, D. H. Rice, M. T. Salam, P. S. Gill, and R. Masood The Significance of EphB4 and EphrinB2 Expression and Survival in Head and Neck Squamous Cell Carcinoma Arch Otolaryngol Head Neck Surg, September 1, 2008; 134(9): 985 - 991. [Abstract] [Full Text] [PDF] A. C. Webler, R. Popp, T. Korff, U. R. Michaelis, C. Urbich, R. Busse, and I. Fleming Cytochrome P450 2C9-Induced Angiogenesis Is Dependent on EphB4 Arterioscler Thromb Vasc Biol, June 1, 2008; 28(6): 1123 - 1129. [Abstract] [Full Text] [PDF] D. Arvanitis and A. Davy Eph/ephrin signaling: networks Genes & Dev., February 15, 2008; 22(4): 416 - 429. [Abstract] [Full Text] [PDF] J. E. Chrencik, A. Brooun, M. I. Recht, G. Nicola, L. K. Davis, R. Abagyan, H. Widmer, E. B. Pasquale, and P. Kuhn Three-dimensional Structure of the EphB2 Receptor in Complex with an Antagonistic Peptide Reveals a Novel Mode of Inhibition J. Biol. Chem., December 14, 2007; 282(50): 36505 - 36513. [Abstract] [Full Text] [PDF]

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