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Research Article Free access | 10.1172/JCI118662

Intravenous somatic gene transfer with antisense tissue factor restores blood flow by reducing tumor necrosis factor-induced tissue factor expression and fibrin deposition in mouse meth-A sarcoma.

Y Zhang, Y Deng, T Wendt, B Liliensiek, A Bierhaus, J Greten, W He, B Chen, V Hach-Wunderle, R Waldherr, R Ziegler, D Männel, D M Stern, and P P Nawroth

Department of Medicine, University of Heidelberg, Germany.

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Department of Medicine, University of Heidelberg, Germany.

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Department of Medicine, University of Heidelberg, Germany.

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Department of Medicine, University of Heidelberg, Germany.

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Department of Medicine, University of Heidelberg, Germany.

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Department of Medicine, University of Heidelberg, Germany.

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Department of Medicine, University of Heidelberg, Germany.

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Department of Medicine, University of Heidelberg, Germany.

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Department of Medicine, University of Heidelberg, Germany.

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Department of Medicine, University of Heidelberg, Germany.

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Department of Medicine, University of Heidelberg, Germany.

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Department of Medicine, University of Heidelberg, Germany.

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Department of Medicine, University of Heidelberg, Germany.

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Department of Medicine, University of Heidelberg, Germany.

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Published May 15, 1996 - More info

Published in Volume 97, Issue 10 on May 15, 1996
J Clin Invest. 1996;97(10):2213–2224. https://doi.org/10.1172/JCI118662.
© 1996 The American Society for Clinical Investigation
Published May 15, 1996 - Version history
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Abstract

Fibrin is deposited on the endothelial cell surface in the vasculature of murine methylcholanthrene A-induced sarcomas after injection of tumor necrosis factor (TNF). Capillary endothelial cells of the tumor vascular bed become positive for tissue factor after TNF injection, based on immunocytochemistry and in situ hybridization. Intravascular clot formation was not dependent on tissue factor derived from tumor cells, since in vessels of tumors not expressing tissue factor, TNF also induced fibrin/fibrinogen deposition. However, the time course of fibrin/fibrinogen deposition after TNF differed in tumors expressing no, little, or greater amounts of tissue factor. Fibrin/fibrinogen deposition was more rapid in tumors in which the neoplastic cells expressed tissue factor than in tumors not expressing tissue factor. In the tumors not expressing tissue factor, activation of coagulation was dependent on TNF-induced synthesis of tissue factor by host cells, i.e., endothelium or monocytes/macrophages. Intravenous somatic gene transfer with tissue factor cDNA in the antisense orientation (but not sense or vector alone) reduced intravascular fibrin/fibrinogen deposition and restored blood flow to the tumor, showing that de novo tissue factor expression is central in TNF-induced activation of the coagulation mechanism.

Version history
  • Version 1 (May 15, 1996): No description
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