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Semin Thromb Hemost 2008; 34(2): 154-160
DOI: 10.1055/s-2008-1079255
© Thieme Medical Publishers

Mechanisms Linking Tumor Cell–Associated Procoagulant Function to Tumor Dissemination

Joseph S. Palumbo1
  • 1Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
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Publication History

Publication Date:
21 July 2008 (online)

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ABSTRACT

There is a persuasive body of evidence suggesting that tissue factor (TF) is a major determinant of tumor progression. In addition to its “traditional” function as the initiator of hemostasis, TF may support tumor progression through signaling mechanisms involving either direct signal transduction through the TF cytoplasmic domain or TF:F VIIa–mediated and TF/F VIIa/F Xa–mediated activation of protease-activated receptors. Whereas TF-mediated signaling events uncoupled from hemostasis may play an important role in tumor dissemination in some contexts, TF-mediated thrombin generation appears to be the major mechanism linking tumor cell–associated TF to metastasis. At least one mechanism coupling thrombin generation to metastatic potential involves the most distal components of the hemostatic system (i.e., platelets, fibrinogen, and factor XIII) and leads to a restriction in natural killer cell–mediated lysis of newly formed micrometastases. A detailed understanding of the mechanisms linking TF and circulating hemostatic system components to tumor progression may lead to novel therapeutic targets for cancer treatment.

KEYWORDS

Hemostatic factors - cancer - NK cells - metastasis

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Joseph S PalumboM.D. 

Cincinnati Children's Hospital Medical Center, Division of Hematology/Oncology

3333 Burnet Ave., Cincinnati, OH 45229

Email: joe.palumbo@cchmc.org