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Blood, 1 May 2004, Vol. 103, No. 9, pp. 3374-3380. Prepublished online as a Blood First Edition Paper on January 22, 2004; DOI 10.1182/blood-2003-07-2234. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-07-2234v1 103/9/3374    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 Hembrough, T. A. Articles by Pribluda, V. S. Search for Related Content PubMed PubMed Citation Articles by Hembrough, T. A. Articles by Pribluda, V. S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Identification and characterization of a very low density lipoprotein receptor-binding peptide from tissue factor pathway inhibitor that has antitumor and antiangiogenic activity Todd A. Hembrough, Jose F. Ruiz, Bonnie M. Swerdlow, Glenn M. Swartz, Hans J. Hammers, Li Zhang, Stacy M. Plum, Mark S. Williams, Dudley K. Strickland, and Victor S. Pribluda From EntreMed, Inc, Rockville, MD; and American Red Cross, Holland Laboratory, Rockville, MD. Tissue factor pathway inhibitor (TFPI) is the major physiologic inhibitor of the extrinsic coagulation pathway. We have previously shown that TFPI is also a potent inhibitor of endothelial proliferation in vitro and of primary and metastatic tumor growth in vivo. Surprisingly, the antitumor activity of TFPI was demonstrated to be independent of its anticoagulant activity, suggesting a possible nonhemostatic mechanism of action for TFPI in these models. This antitumor mechanism may involve the very low density lipoprotein (VLDL) receptor because the in vitro antiproliferative activity of TFPI is mediated through interaction with the VLDL receptor. In the current study, we identify a 23-amino acid fragment of TFPI (TFPIc23) localized to the C-terminus, which mediates binding to the VLDL receptor. The TFPIc23 peptide inhibits endothelial cell proliferation through an apoptotic mechanism and blocks vessel outgrowth in the in vitro assays, and this activity is mediated through interaction with the VLDL receptor. In vivo, this peptide potently inhibits angiogenesis in Matrigel and chick chorioallantoic membrane models and also inhibits metastatic tumor growth. Our data demonstrate that this VLDL receptor-binding fragment of the TFPI molecule has apoptotic, antiangiogenic, and antitumor activity and suggests a possible mechanism whereby TFPI can regulate angiogenesis and tumor growth independently of its anticoagulant activity. (Blood. 2004;103: 3374-3380) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Pan, T. A. White, T. A. Witt, A. Chiriac, C. S. Mueske, and R. D. Simari Vascular-Directed Tissue Factor Pathway Inhibitor Overexpression Regulates Plasma Cholesterol and Reduces Atherosclerotic Plaque Development Circ. Res., September 25, 2009; 105(7): 713 - 720. [Abstract] [Full Text] [PDF] W. Hu, A. Jiang, J. Liang, H. Meng, B. Chang, H. Gao, and X. Qiao Expression of VLDLR in the Retina and Evolution of Subretinal Neovascularization in the Knockout Mouse Model's Retinal Angiomatous Proliferation Invest. Ophthalmol. Vis. Sci., January 1, 2008; 49(1): 407 - 415. [Abstract] [Full Text] [PDF] J. Ruiz, D. Kouiavskaia, M. Migliorini, S. Robinson, E. L. Saenko, N. Gorlatova, D. Li, D. Lawrence, B. T. Hyman, K. H. Weisgraber, et al. The apoE isoform binding properties of the VLDL receptor reveal marked differences from LRP and the LDL receptor J. Lipid Res., August 1, 2005; 46(8): 1721 - 1731. [Abstract] [Full Text] [PDF]

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