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Blood, 1 June 2007, Vol. 109, No. 11, pp. 4753-4760. Prepublished online as a Blood First Edition Paper on February 20, 2007; DOI 10.1182/blood-2006-12-063933. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-12-063933v1 109/11/4753    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 Scehnet, J. S Articles by Gill, P. S Search for Related Content PubMed PubMed Citation Articles by Scehnet, J. S Articles by Gill, P. S Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 21, 2006 Accepted February 6, 2007 Inhibition of Dll4 mediated signaling induces proliferation of immature vessels and results in poor tissue perfusion Jeffrey S Scehnet, Weidong Jiang, S Ram Kumar, Valery Krasnoperov, Alexandre Trindade, Rui Benedito, Dusan Djokovic, Cristina Borges, Eric J Ley, Antonio Duarte, and Parkash S Gill* Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA, United States Vasgene Therapeutics, Los Angeles, CA, United States Department of Surgery, University of Southern California Keck School of Medicine, Los Angeles, CA, United States CIISA, Faculdade de Medicina Veterinaria, Technical University of Lisbon, Lisbon, Portugal Instituto Gulbenkian de Ciencia, Oeiras, Portugal Department of Colorectal Surgery, University of Southern California Keck School of Medicine, Los Angeles, CA, United States Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, United States * Corresponding author; email: parkashg{at}usc.edu. Vascular development is dependent on various growth factors and certain modifiers critical for providing arterial or venous identity, interaction with the surrounding stroma and tissues, hierarchical network formation, and recruitment of pericytes. Notch receptors and ligands (Jagged and Delta-like) play a critical role in this process in addition to VEGF. Dll4 is one of the Notch ligands that regulate arterial specification and maturation events. In the current study, we have shown that loss of function by either targeted allele deletion or use of a soluble form of Dll4 extracellular domain leads to inhibition of Notch signaling, resulting in increased vascular proliferation but defective maturation. Newly forming vessels have thin caliber, a markedly reduced vessel lumen, markedly reduced pericyte recruitment and deficient vascular perfusion. sDll4 similarly induced defective vascular response in tumor implants leading to reduced tumor growth. Interference with Dll4-Notch signaling may be particularly desirable in tumors which have highly induced Dll4-Notch pathway. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M.-T. Huang, Y.-S. Dai, Y.-B. Chou, Y.-H. Juan, C.-C. Wang, and B.-L. Chiang Regulatory T Cells Negatively Regulate Neovasculature of Airway Remodeling via DLL4-Notch Signaling J. Immunol., October 1, 2009; 183(7): 4745 - 4754. [Abstract] [Full Text] [PDF] T. Rauen, U. Raffetseder, B. C. Frye, S. Djudjaj, P. J. T. Muhlenberg, F. Eitner, U. Lendahl, J. Bernhagen, S. Dooley, and P. R. Mertens YB-1 Acts as a Ligand for Notch-3 Receptors and Modulates Receptor Activation J. Biol. Chem., September 25, 2009; 284(39): 26928 - 26940. [Abstract] [Full Text] [PDF] N. Skuli, L. Liu, A. Runge, T. Wang, L. Yuan, S. Patel, L. Iruela-Arispe, M. C. Simon, and B. 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