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Blood, 19 March 2009, Vol. 113, No. 12, pp. 2835-2842. Prepublished online as a Blood First Edition Paper on November 25, 2008; DOI 10.1182/blood-2008-06-159541. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2008-06-159541v1 113/12/2835    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 Klement, G. L. Articles by Folkman, J. Search for Related Content PubMed PubMed Citation Articles by Klement, G. L. Articles by Folkman, J. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 2, 2008 Accepted October 14, 2008 Platelets actively sequester angiogenesis regulators Giannoula Lakka Klement*, Tai-Tung Yip, Flavia Cassiola, Lena Kikuchi, David Cervi, Vladimir Podust, Joseph E Italiano, Erin Wheatley, Abdo Abou-Slaybi, Elise Bender, Nava Almog, Mark Kieran, and Judah Folkman Children's Hospital, Boston, MA, United States Ciphergen Biosystems Inc., Fremont, CA, United States Brigham and Women's Hospital, Boston, MA, United States Dana-Farber Cancer Institute, Boston, MA, United States * Corresponding author; email: giannoula_klement{at}dfci.harvard.edu. Clinical trials with antiangiogenic agents have not been able to validate plasma or serum levels of angiogenesis regulators as reliable markers of cancer presence or therapeutic response. We recently reported that platelets contain numerous proteins that regulate angiogenesis. We now show that accumulation of angiogenesis regulators in platelets of animals bearing malignant tumors exceeds significantly their concentration in plasma or serum, as well as their levels in platelets from non-tumor bearing animals. This process is selective, as platelets do not take up a proportional amount of other plasma proteins (e.g. albumin), even though these may be present at higher concentrations. We also find that VEGF-enriched Matrigel pellets implanted subcutaneously into mice or the minute quantities of VEGF secreted by microscopic subcutaneous tumors (0.5-1 mm3) result in an elevation of VEGF levels in platelets, without any changes in its plasma levels. The profile of other angiogenesis regulatory proteins (e.g. PDGF, bFGF) sequestered by platelets also reflects the presence of tumors in vivo before they can be macroscopically evident. The ability of platelets to selectively take up angiogenesis regulators in cancer bearing hosts may have implications for the diagnosis and management many angiogenesis-related diseases, and provide a guide for antiangiogenic therapies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: To give and take — life of a platelet Jan Palmblad Blood 2009 113: 2617. [Full Text] [PDF] This article has been cited by other articles: J. Palmblad To give and take -- life of a platelet Blood, March 19, 2009; 113(12): 2617 - 2617. [Full Text] [PDF]

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