Tissue Factor and Fibrin in Tumor Angiogenesis

Patricia M. Fernandez; Steven R. Patierno; Frederick R. Rickles

doi:10.1055/s-2004-822969

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2004; 30(1): 31-44
DOI: 10.1055/s-2004-822969

Tissue Factor and Fibrin in Tumor Angiogenesis

Patricia M. Fernandez¹ ^, ² , Steven R. Patierno¹ ^, ² , Frederick R. Rickles³

¹Department of Pharmacology, George Washington University Medical Center, Washington, DC, U.S.
²Department of Urology, George Washington University Medical Center, Washington, DC, U.S.
³Professor, Departments of Medicine and Pediatrics, George Washington University Medical Center, Washington, DC, U.S.

Abstract

The hypercoagulability exhibited by most cancer patients leads to serious complications such as venous thromboembolism and contributes to the pathogenesis of tumor growth and metastasis by promoting angiogenesis. The key player in this vicious cycle is tissue factor (TF), the initiator of blood coagulation. Although TF normally safeguards vascular integrity by inducing hemostasis upon injury, abnormal expression of TF in different tumors and related vascular endothelial cells contributes to unnecessary clot formation in cancer patients. Clotting-dependent induction of tumor angiogenesis is primarily mediated by TF-induced generation of thrombin and subsequent deposition of cross-linked fibrin. A cross-linked fibrin network provides a provisional proangiogenic matrix that facilitates blood vessel infiltration. Clotting-independent mechanisms of TF-induced tumor angiogenesis have also been described, mediated primarily by the cytoplasmic tail of the TF receptor. TF activation could contribute to the venous thromboembolism that has been reported as a complication of the use of novel antiangiogenic agents in combination with chemotherapy. Anticoagulants, such as low-molecular-weight heparin, may act to prevent these complications both by interfering with TF-mediated activation of clotting and by directly down-regulating angiogenesis. Thus, TF may prove to be a novel target for cancer therapy.

KEYWORDS

Tissue factor - fibrin - angiogenesis - low-molecular-weight heparin - clot

Full Text

References

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