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This Article Full Text Full Text (PDF) 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 Bugge, T. H. Search for Related Content PubMed PubMed Citation Articles by Palumbo, J. S. Articles by Bugge, T. H. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Focus on Hematology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 November 2000, Vol. 96, No. 10, pp. 3302-3309 FOCUS ON HEMATOLOGY Fibrinogen is an important determinant of the metastatic potential of circulating tumor cells Joseph S. Palumbo, Keith W. Kombrinck, Angela F. Drew, Timothy S. Grimes, John H. Kiser, Jay L. Degen, and Thomas H. Bugge From the Divisions of Hematology/Oncology and Developmental Biology, Children's Hospital Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH. Detailed studies of tumor cell-associated procoagulants and fibrinolytic factors have implied that local thrombin generation and fibrin deposition and dissolution may be important in tumor growth and dissemination. To directly determine whether fibrin(ogen) or plasmin(ogen) are determinants of the metastatic potential of circulating tumor cells, this study examined the impact of genetic deficits in each of these key hemostatic factors on the hematogenous pulmonary metastasis of 2 established murine tumors, Lewis lung carcinoma and the B16-BL6 melanoma. In both tumor models, fibrinogen deficiency strongly diminished, but did not prevent, the development of lung metastasis. The quantitative reduction in metastasis in fibrinogen-deficient mice was not due to any appreciable difference in tumor stroma formation or tumor growth. Rather, tumor cell fate studies indicated an important role for fibrin(ogen) in sustained adhesion and survival of tumor cells within the lung. The specific thrombin inhibitor, hirudin, further diminished the metastatic potential of circulating tumor cells in fibrinogen-deficient mice, although the inhibitor had no apparent effect on tumor cell proliferation in vitro. The absence of plasminogen and plasmin-mediated fibrinolysis had no significant impact on hematogenous metastasis. The authors concluded that fibrin(ogen) is a critical determinant of the metastatic potential of circulating tumor cells. Furthermore, thrombin appears to facilitate tumor dissemination through at least one fibrin(ogen)-independent mechanism. These findings suggest that therapeutic strategies focusing on multiple distinct hemostatic factors might be beneficial in the containment of tumor metastasis. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. S. Alves, M. M. Burdick, S. N. Thomas, P. Pawar, and K. Konstantopoulos The dual role of CD44 as a functional P-selectin ligand and fibrin receptor in colon carcinoma cell adhesion Am J Physiol Cell Physiol, April 1, 2008; 294(4): C907 - C916. [Abstract] [Full Text] [PDF] S. W. Jackson, T. Hoshi, Y. Wu, X. Sun, K. Enjyoji, E. Cszimadia, C. Sundberg, and S. C. Robson Disordered Purinergic Signaling Inhibits Pathological Angiogenesis in Cd39/Entpd1-Null Mice Am. J. Pathol., October 1, 2007; 171(4): 1395 - 1404. [Abstract] [Full Text] [PDF] J.-S. Wang, C.-Y. Chang, S.-E. Chow, Y.-W. Chen, and C.-M. 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