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Blood, 9 July 2009, Vol. 114, No. 2, pp. 237-247. Prepublished online as a Blood First Edition Paper on April 1, 2009; DOI 10.1182/blood-2008-12-196451. This Article Full Text (PDF) Supplemental Figures and Videos Additional Supplemental Videos All Versions of this Article: blood-2008-12-196451v1 114/2/237    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 Stratman, A. N. Articles by Davis, G. E. Search for Related Content PubMed PubMed Citation Articles by Stratman, A. N. Articles by Davis, G. E. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 23, 2008 Accepted March 26, 2009 Endothelial cell lumen and vascular guidance tunnel formation requires MT1-MMP-dependent proteolysis in 3D collagen matrices Amber N. Stratman, W. Brian Saunders, Anastasia Sacharidou, Wonshill Koh, Kevin E. Fisher, David C. Zawieja, Michael J. Davis, and George E. Davis* Department of Medical Pharmacology and Physiology, School of Medicine, Dalton Cardiovascular Center, University of Missouri-Columbia, Columbia, MO, United States Department of Systems Biology and Translational Medicine, School of Medicine, Texas A&M University Health Science Center, College Station, TX, United States Department of Pathology and Anatomical Sciences, School of Medicine, Dalton Cardiovascular Center, University of Missouri-Columbia, Columbia, MO, United States * Corresponding author; email: davisgeo{at}health.missouri.edu. Here we show that endothelial cells (EC) require matrix type 1-metalloproteinase (MT1-MMP) for the formation of lumens and tube networks in three-dimensional (3D) collagen matrices. A fundamental consequence of EC lumen formation is the generation of vascular guidance tunnels within collagen matrices through an MT1-MMP-dependent proteolytic process. Vascular guidance tunnels represent a conduit for EC motility within these spaces (a newly remodeled 2D matrix surface) to both assemble and remodel tube structures. Interestingly, it appears that twice as many tunnel spaces are created than are occupied by tube networks after several days of culture. Following tunnel formation, these spaces represent a 2D migratory surface within 3D collagen matrices allowing for EC migration in an MMP-independent fashion. Blockade of EC lumenogenesis using inhibitors that interfere with the process (i.e. integrin, MMP, PKC, Src) completely abrogates the formation of vascular guidance tunnels. Thus, the MT1-MMP-dependent proteolytic process which creates tunnel spaces is directly and functionally coupled to the signaling mechanisms required for EC lumen and tube network formation. In summary, a fundamental and previously unrecognized purpose of EC tube morphogenesis is to create networks of matrix conduits that are necessary for EC migration and tube remodeling events critical to blood vessel assembly. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. E. Fisher, A. Sacharidou, A. N. Stratman, A. M. Mayo, S. B. Fisher, R. D. Mahan, M. J. Davis, and G. E. Davis MT1-MMP- and Cdc42-dependent signaling co-regulate cell invasion and tunnel formation in 3D collagen matrices J. Cell Sci., December 15, 2009; 122(24): 4558 - 4569. [Abstract] [Full Text] [PDF] A. N. Stratman, K. M. Malotte, R. D. Mahan, M. J. Davis, and G. E. Davis Pericyte recruitment during vasculogenic tube assembly stimulates endothelial basement membrane matrix formation Blood, December 3, 2009; 114(24): 5091 - 5101. [Abstract] [Full Text] [PDF]

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