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Blood, 1 January 2005, Vol. 105, No. 1, pp. 178-185. Prepublished online as a Blood First Edition Paper on September 14, 2004; DOI 10.1182/blood-2004-06-2272. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-06-2272v1 105/1/178    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 Palumbo, J. S. Articles by Degen, J. L. Search for Related Content PubMed PubMed Citation Articles by Palumbo, J. S. Articles by Degen, J. L. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell–mediated elimination of tumor cells Joseph S. Palumbo, Kathryn E. Talmage, Jessica V. Massari, Christine M. La Jeunesse, Matthew J. Flick, Keith W. Kombrinck, Markéta Jirousková, and Jay L. Degen From the Divisions of Hematology/Oncology and Developmental Biology, Children's Hospital Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH; and The Rockefeller University, New York, NY. To test the hypothesis that platelet activation contributes to tumor dissemination, we studied metastasis in mice lacking Gq, a G protein critical for platelet activation. Loss of platelet activation resulted in a profound diminution in both experimental and spontaneous metastases. Analyses of the distribution of radiolabeled tumor cells demonstrated that platelet function, like fibrinogen, significantly improved the survival of circulating tumor cells in the pulmonary vasculature. More detailed studies showed that the increase in metastatic success conferred by either platelets or fibrinogen was linked to natural killer cell function. Specifically, the pronounced reduction in tumor cell survival observed in fibrinogen- and Gq-deficient mice relative to control animals was eliminated by the immunologic or genetic depletion of natural killer cells. These studies establish an important link between hemostatic factors and innate immunity and indicate that one mechanism by which the platelet-fibrin(ogen) axis contributes to metastatic potential is by impeding natural killer cell elimination of tumor cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: A platelet cloak for tumor cells Hartmut Weiler Blood 2005 105: 5-6. [Full Text] [PDF] This article has been cited by other articles: T. Sousou and A. A. Khorana New Insights Into Cancer-Associated Thrombosis Arterioscler. Thromb. Vasc. Biol., March 1, 2009; 29(3): 316 - 320. [Abstract] [Full Text] [PDF] C. S. Alves, S. Yakovlev, L. Medved, and K. Konstantopoulos Biomolecular Characterization of CD44-Fibrin(ogen) Binding: DISTINCT MOLECULAR REQUIREMENTS MEDIATE BINDING OF STANDARD AND VARIANT ISOFORMS OF CD44 TO IMMOBILIZED FIBRIN(OGEN) J. Biol. Chem., January 9, 2009; 284(2): 1177 - 1189. [Abstract] [Full Text] [PDF] N. Li Platelet-lymphocyte cross-talk J. Leukoc. Biol., May 1, 2008; 83(5): 1069 - 1078. [Abstract] [Full Text] [PDF] N. Pacienza, R. G. Pozner, G. A. Bianco, L. P. D'Atri, D. O. Croci, S. Negrotto, E. Malaver, R. M. Gomez, G. A. Rabinovich, and M. 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W. Kombrinck, Z. Hu, K. A. Barney, and J. L. Degen Tumor cell-associated tissue factor and circulating hemostatic factors cooperate to increase metastatic potential through natural killer cell-dependent and-independent mechanisms Blood, July 1, 2007; 110(1): 133 - 141. [Abstract] [Full Text] [PDF] S. Jain, M. Zuka, J. Liu, S. Russell, J. Dent, J. A. Guerrero, J. Forsyth, B. Maruszak, T. K. Gartner, B. Felding-Habermann, et al. Platelet glycoprotein Ib{alpha} supports experimental lung metastasis PNAS, May 22, 2007; 104(21): 9024 - 9028. [Abstract] [Full Text] [PDF] M. Bloomston, J. X. Zhou, A. S. Rosemurgy, W. Frankel, C. A. Muro-Cacho, and T. J. Yeatman Fibrinogen {gamma} Overexpression in Pancreatic Cancer Identified by Large-scale Proteomic Analysis of Serum Samples. Cancer Res., March 1, 2006; 66(5): 2592 - 2599. [Abstract] [Full Text] [PDF] T. A. Guise Thromboembolism to Metastasis: The Platelet-Lysophosphatidic Acid Connection IBMS BoneKEy, March 1, 2005; 2(3): 12 - 16. 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