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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 (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 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 Articles by Reijerkerk, A. Search for Related Content PubMed PubMed Citation Articles by Gebbink, M. F Articles by Reijerkerk, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 5, 2004 Accepted May 7, 2004 Do anti-angiogenic protein fragments have amyloid properties? Martijn F Gebbink*, Emile E Voest, and Arie Reijerkerk Haematology, University Medical Center Utrecht, Utrecht, The Netherlands Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands * Corresponding author; email: m.gebbink{at}azu.nl. Tumor growth requires proteolytic activity. As a consequence, protein breakdown products are present in the circulation of cancer patients. Within the past decade a large number of proteolytic fragments have been identified that inhibit angiogenesis and tumor growth. The mechanism(s) 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's 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. Since the presence of cross- structure is the common denominator in tPA-binding ligands, we hypothesize that these endogenous anti-angiogenic proteolytic fragments share features with amyloidogenic polypeptides. We postulate that the cross- structural fold, is present in these anti-angiogenic 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. 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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