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Thromb Haemost 2002; 87(06): 930-936
DOI: 10.1055/s-0037-1613114
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Schattauer GmbH

Tissue Factor Pathway Inhibitor Reduces Experimental Lung Metastasis of B16 Melanoma[*]

Ali Amirkhosravi
1   Clinical and Research Laboratories, Florida Hospital Cancer Institute, Florida Hospital, Orlando, FL
,
Todd Meyer
1   Clinical and Research Laboratories, Florida Hospital Cancer Institute, Florida Hospital, Orlando, FL
,
Jen-Yea Chang
2   Division of Hematology and Oncology, Department of Medicine, School of Medicine, The University of North Carolina, Chapel Hill, NC, USA
,
Mildred Amaya
1   Clinical and Research Laboratories, Florida Hospital Cancer Institute, Florida Hospital, Orlando, FL
,
Farooq Siddiqui
1   Clinical and Research Laboratories, Florida Hospital Cancer Institute, Florida Hospital, Orlando, FL
,
Hina Desai
1   Clinical and Research Laboratories, Florida Hospital Cancer Institute, Florida Hospital, Orlando, FL
,
John L. Francis
1   Clinical and Research Laboratories, Florida Hospital Cancer Institute, Florida Hospital, Orlando, FL
› Author Affiliations
Further Information

Publication History

Received 19 November 2001

Accepted after revision 11 February 2002

Publication Date:
08 December 2017 (online)

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Summary

The importance of tissue factor (TF) in tumor biology has been highlighted by studies suggesting its involvement in cell signaling, metastasis and angiogenesis. Since many animal studies have shown that anticoagulant therapy can reduce experimental metastasis, we studied whether the natural inhibitor of TF-mediated blood coagulation, Tissue Factor Pathway Inhibitor (TFPI), might be similarly effective. Using a murine experimental model, we found that intravenous injection of recombinant murine TFPI immediately before introduction of tumor cells reduced metastasis by 83% (P <0.001). B16 murine melanoma cells stably transfected with a TFPI expression vector exhibited reduced lung seeding following intravenous injection by 81% (P <0.001) compared with controls. No difference in primary tumor growth was observed between TFPI+ and control cells. Mice receiving intravenous somatic gene transfer of sense TFPI expression vector developed 78% fewer lung nodules than controls (P <0.05). We conclude that TFPI has significant anti-metastatic activity in this experimental model.

Keywords

TFPI - metastasis - melanoma - coagulation - tumor

* Presented at the International Society on Thrombosis and Haemostasis Meeting 2001, Paris, France


 

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