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Blood, 2 April 2009, Vol. 113, No. 14, pp. 3371-3374. Prepublished online as a Blood First Edition Paper on February 2, 2009; DOI 10.1182/blood-2008-05-159434. This Article Full Text (PDF) All Versions of this Article: blood-2008-05-159434v1 113/14/3371    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 Bezuhly, M. Articles by Liwski, R. S. Search for Related Content PubMed PubMed Citation Articles by Bezuhly, M. Articles by Liwski, R. S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 28, 2008 Accepted January 21, 2009 Role of activated protein C and its receptor in inhibition of tumor metastasis Michael Bezuhly, Robyn Cullen, Charles T. Esmon, Steven F. Morris, Kenneth A. West, Brent Johnston, and Robert S. Liwski* Department of Anatomy and Neurobiology, Dalhousie University, Halifax, NS, Canada Department of Pathology, Dalhousie University, Halifax, NS, Canada Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States Department of Surgery, Dalhousie University, Halifax, NS, Canada Department of Medicine, Dalhousie University, Halifax, NS, Canada Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada * Corresponding author; email: rliwski{at}dal.ca. Engagement of endothelial protein C receptor (EPCR) by activated protein C (aPC) decreases expression of endothelial adhesion molecules implicated in tumor-endothelium interactions. We examined the role of the aPC/EPCR pathway on tumor migration and metastasis. In vitro, B16-F10 melanoma cells showed decreased adhesion to and transmigration through endothelium treated with recombinant human aPC (rhaPC). In murine B16-F10 metastasis models, transgenic EPCR overexpressing (Tie2-EPCR) mice exhibited marked reductions in liver (50%) and lung (92%) metastases compared to wildtype (WT) animals. Intravital imaging revealed reduced B16-F10 entrapment within livers of Tie2-EPCR compared to WT mice. A similar reduction was observed in WT mice treated with rhaPC. Strikingly, rhaPC treatment resulted in a 44% reduction in lung metastases. This was associated with decreased lung P-selectin and TNF- mRNA levels. These findings support an important role for the aPC/EPCR pathway in reducing metastasis via inhibition of tumor cell adhesion and transmigration. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Schaffner and W. Ruf Tissue Factor and PAR2 Signaling in the Tumor Microenvironment Arterioscler Thromb Vasc Biol, December 1, 2009; 29(12): 1999 - 2004. [Abstract] [Full Text] [PDF] G. L. Van Sluis, T. M.H. Niers, C. T. Esmon, W. Tigchelaar, D. J. Richel, H. R. Buller, C. J.F. Van Noorden, and C. A. Spek Endogenous activated protein C limits cancer cell extravasation through sphingosine-1-phosphate receptor 1-mediated vascular endothelial barrier enhancement Blood, August 27, 2009; 114(9): 1968 - 1973. [Abstract] [Full Text] [PDF]

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