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Blood, 15 September 2004, Vol. 104, No. 6, pp. 1601-1605. Prepublished online as a Blood First Edition Paper on May 27, 2004; DOI 10.1182/blood-2004-02-0433. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-02-0433v1 104/6/1601    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 Gebbink, M. F. B. G. Articles by Reijerkerk, A. Search for Related Content PubMed PubMed Citation Articles by Gebbink, M. F. B. G. Articles by Reijerkerk, A. Related Collections Perspectives Hematopoiesis and Stem Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PERSPECTIVES Do antiangiogenic protein fragments have amyloid properties? Martijn F. B. G. Gebbink, Emile E. Voest, and Arie Reijerkerk From the Laboratory of Thrombosis and Hemostasis, Department of Hematology and Department of Medical Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands. Abstract Tumor growth requires proteolytic activity. As a consequence, protein breakdown products are present in the circulation of patients with cancer. Within the past decade a large number of proteolytic fragments have been identified that inhibit angiogenesis and tumor growth. The mechanism of action of these inhibitors is still poorly understood. We recently found that the effects of the angiogenesis inhibitor endostatin on endothelial cells is critically dependent on the presence of cross- structure, a structure also present in amyloidogenic polypeptides in plaques of patients with amyloidosis, such as Alzheimer disease. We also showed that cross- structure containing endostatin is a ligand for tissue-type plasminogen activator (tPA). We noted that many angiogenesis inhibitors stimulate tPA-mediated plasminogen activation. Because the presence of cross- structure is the common denominator in tPA-binding ligands, we hypothesize that these endogenous antiangiogenic proteolytic fragments share features with amyloidogenic polypeptides. We postulate that the cross- structural fold is present in these antiangiogenic polypeptide fragments and that this structure mediates the inhibitory effects. The hypothesis provides new insights in the potential mechanisms of these angiogenesis inhibitors and offers opportunities to improve their use. (Blood. 2004;104:1601-1605) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. H. G. Hansma, H. J. Broxterman, I. van der Horst, Y. Yuana, E. Boven, G. Giaccone, H. M. Pinedo, and K. Hoekman Recombinant human endostatin administered as a 28-day continuous intravenous infusion, followed by daily subcutaneous injections: a phase I and pharmacokinetic study in patients with advanced cancer Ann. Onc., October 1, 2005; 16(10): 1695 - 1701. [Abstract] [Full Text] [PDF]

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