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Blood, 15 October 2003, Vol. 102, No. 8, pp. 2819-2827. Prepublished online as a Blood First Edition Paper on June 26, 2003; DOI 10.1182/blood-2003-03-0881. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-03-0881v1 102/8/2819    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 Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Plasminogen supports tumor growth through a fibrinogen-dependent mechanism linked to vascular patency Joseph S. Palumbo, Kathryn E. Talmage, Hong Liu, Christine M. La Jeunesse, David P. Witte, and Jay L. Degen From the Divisions of Hematology/Oncology, Developmental Biology, and Pathology, Children's Hospital Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH. The growth of Lewis lung carcinoma (LLC) was sustained in plasminogen-deficient mice when transplanted into the dorsal skin but was dramatically suppressed in another anatomic location, the footpad. This unanticipated negative effect of plasminogen deficiency on footpad tumor growth was entirely relieved by superimposing a deficit in fibrinogen. This finding was not simply an unusual feature of LLC tumors—T241 fibrosarcoma growth in the footpad was also restricted by plasminogen deficiency in a fibrinogen-dependent manner. The probable mechanistic basis for suppression of tumor growth was revealed through transmission electron microscopy studies of tumor tissues. Occlusive microvascular thrombi were commonplace within footpad tumors from plasminogen-deficient mice, whereas no such lesions were observed within either dorsal skin tumors from plasminogen-deficient mice or footpad tumors from mice that also lacked fibrinogen. The data infer that tumor growth in the footpad of plasminogen-deficient mice is compromised as a function of the formation and persistence of vaso-occlusive thrombi that limit tumor blood supply. These studies indicate that plasminogen and fibrinogen can serve as critical determinants of tumor growth, but their relative importance is dependent on the tumor microenvironment. Furthermore, these studies suggest that one target of plasmin(ogen) relevant to tumor progression in vivo is intravascular fibrin. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Location, location, location Edward F. Plow Blood 2003 102: 2709. [Full Text] [PDF] This article has been cited by other articles: R. Das, T. Burke, and E. F. Plow Histone H2B as a functionally important plasminogen receptor on macrophages Blood, November 15, 2007; 110(10): 3763 - 3772. [Abstract] [Full Text] [PDF] A.-J. Cheng, L.-C. Chen, K.-Y. Chien, Y.-J. Chen, J. T.-C. Chang, H.-M. Wang, C.-T. Liao, and I-H. Chen Oral Cancer Plasma Tumor Marker Identified with Bead-Based Affinity-Fractionated Proteomic Technology Clin. Chem., December 1, 2005; 51(12): 2236 - 2244. [Abstract] [Full Text] [PDF] J. S. Palumbo, K. E. Talmage, J. V. Massari, C. M. La Jeunesse, M. J. Flick, K. W. Kombrinck, M. Jirouskova, and J. L. Degen Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells Blood, January 1, 2005; 105(1): 178 - 185. [Abstract] [Full Text] [PDF]

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