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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-02-0582. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-02-0582v1 101/5/1857    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Wajih, N. Articles by Sane, D. C. Search for Related Content PubMed PubMed Citation Articles by Wajih, N. Articles by Sane, D. C. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 March 2003, Vol. 101, No. 5, pp. 1857-1863 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Angiostatin selectively inhibits signaling by hepatocyte growth factor in endothelial and smooth muscle cells Nadeem Wajih and David C. Sane From the Wake Forest University School of Medicine, Section of Cardiology, Winston-Salem, NC. Angiostatin, an inhibitor of angiogenesis, contains 3 to 4 kringle domains that are derived from proteolytic cleavage of plasminogen. The antiangiogenic effects of angiostatin occur, in part, from its inhibition of endothelial cell surface adenosine triphosphate synthase, integrin functions, and pericellular proteolysis. Angiostatin has structural similarities to hepatocyte growth factor (HGF; "scatter factor"), a promoter of angiogenesis, that induces proliferation and migration of both endothelial and smooth muscle cells via its cell surface receptor, c-met. We hypothesized that angiostatin might block HGF-induced signaling in endothelial and smooth muscle cells. Angiostatin inhibited HGF-induced phosphorylation of c-met, Akt, and ERK1/2. Angiostatin also significantly inhibited proliferation of human umbilical vein endothelial cells (HUVECs) induced by HGF. In contrast, angiostatin did not inhibit vascular endothelial growth factor (VEGF)-or basic fibroblast growth factor (bFGF)-induced signaling events or HUVEC proliferation. Angiostatin bound to immobilized truncated c-met produced by A431 cells and could be immunoprecipitated as a complex with soluble c-met. HGF inhibited the binding of 125I-angiostatin to HUVECs. Soluble c-met, produced by several tumor cell lines, could inhibit the antiangiogenic effect of angiostatin. The disruption of HGF/c-met signaling is a novel mechanism for the antiangiogenic effect of angiostatin. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T.-Y. Lee, S. Muschal, E. A. Pravda, J. Folkman, A. Abdollahi, and K. Javaherian Angiostatin regulates the expression of antiangiogenic and proapoptotic pathways via targeted inhibition of mitochondrial proteins Blood, August 27, 2009; 114(9): 1987 - 1998. [Abstract] [Full Text] [PDF] A. Bratt, O. Birot, I. Sinha, N. Veitonmaki, K. Aase, M. Ernkvist, and L. Holmgren Angiomotin Regulates Endothelial Cell-Cell Junctions and Cell Motility J. Biol. Chem., October 14, 2005; 280(41): 34859 - 34869. [Abstract] [Full Text] [PDF] V. Leksa, S. Godar, H. B. Schiller, E. Fuertbauer, A. Muhammad, K. Slezakova, V. Horejsi, P. Steinlein, U. H. Weidle, B. R. Binder, et al. TGF-{beta}-induced apoptosis in endothelial cells mediated by M6P/IGFII-R and mini-plasminogen J. Cell Sci., October 1, 2005; 118(19): 4577 - 4586. [Abstract] [Full Text] [PDF] M. S. Aguzzi, C. Giampietri, F. De Marchis, F. Padula, R. Gaeta, G. Ragone, M. C. Capogrossi, and A. Facchiano RGDS peptide induces caspase 8 and caspase 9 activation in human endothelial cells Blood, June 1, 2004; 103(11): 4180 - 4187. [Abstract] [Full Text] [PDF] J.-H. Ahn, J.-S. Kim, H.-K. Yu, H.-J. Lee, and Y. Yoon A Truncated Kringle Domain of Human Apolipoprotein(a) Inhibits the Activation of Extracellular Signal-regulated Kinase 1 and 2 through a Tyrosine Phosphatase-dependent Pathway J. Biol. Chem., May 21, 2004; 279(21): 21808 - 21814. [Abstract] [Full Text] [PDF] A. Ikai, R. K. Riemer, X. Ma, O. Reinhartz, F. L. Hanley, and V. M. Reddy Pulmonary expression of the hepatocyte growth factor receptor c-Met shifts from medial to intimal layer after cavopulmonary anastomosis J. Thorac. Cardiovasc. Surg., May 1, 2004; 127(5): 1442 - 1449. [Abstract] [Full Text] [PDF] T. Levchenko, K. Aase, B. Troyanovsky, A. Bratt, and L. Holmgren Loss of responsiveness to chemotactic factors by deletion of the C-terminal protein interaction site of angiomotin J. Cell Sci., September 15, 2003; 116(18): 3803 - 3810. [Abstract] [Full Text] [PDF]

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