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 sarcomas

Zhang, YM and Deng, YH and Wendt, T and Liliensiek, B and Bierhaus, A and Greten, J and He, W and Chen, BS and HachWunderle, V and Waldherr, R and Ziegler, R and Mannel, D and Stern, DM and Nawroth, PP (1996) 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 sarcomas. JOURNAL OF CLINICAL INVESTIGATION, 97 (10). pp. 2213-2224. ISSN 0021-9738, 1558-8238

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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 dot 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.

Item Type: Article
Uncontrolled Keywords: FACTOR CACHECTIN; ENDOTHELIAL-CELLS; PROCOAGULANT ACTIVITY; POLYPEPTIDE; INTERLEUKIN-1; HYBRIDIZATION; TRANSCRIPTION; IMMUNIZATION; PERMEABILITY; MECHANISM; tissue factor; endothelium; gene transfer
Depositing User: Dr. Gernot Deinzer
Last Modified: 19 Oct 2022 08:35
URI: https://pred.uni-regensburg.de/id/eprint/51706

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