Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice

Youming Zhang, Youhua Deng, Thomas Luther, Martin Müller, Reinhard Ziegler, Rüdiger Waldherr, David Stern, Peter Paul Nawroth

Research output: Contribution to journalArticle

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Abstract

Meth-A sarcoma cells were stable transfected to overexpress (sense construct) or underexpress (antisense construct) tissue factor. In vitro, there was no difference in plating efficiency or growth between these cell lines. In vivo, tumor cells transfected to overexpress tissue factor grew more rapidly, and established larger and more vascularized tumors than control transfectants. Antisense transfectants grew the slowest and were the least vascularized. Anticoagulation of mice with warfarin did not alter the difference between these tumor lines. Tumor cells overexpressing tissue factor released more (compared with control transfectants) mitogenic activity for endothelial cells in parallel with enhanced transcription of vascular permeability factor/vascular endothelial cell growth factor (VEGF/VPF), and diminished transcription of thrombospondin (TSP2), a molecule with anti- angiogenic properties. Antisense tissue factor transfectants, while releasing the lowest amount of mitogenic activity, had increased thrombospondin and decreased VEGF/VPF transcription compared with control transfectants or wild- type cells. Experiments with these sense, antisense, truncated sense, or vector tumor lines gave comparable results in complete medium, serum free medium or in the presence of hirudin, indicating that the activation of the coagulation mechanism was not likely to be responsible for changes in tumor cell properties. These results suggest that tissue factor regulates angiogenic properties of tumor cells by altering the production of growth regulatory molecules of endothelium by a mechanism distinct from tissue factor activation of the coagulation mechanism.

Original languageEnglish (US)
Pages (from-to)1320-1327
Number of pages8
JournalJournal of Clinical Investigation
Volume94
Issue number3
DOIs
StatePublished - Jan 1 1994

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Thromboplastin
Vascular Endothelial Growth Factor A
Neoplasms
Thrombospondins
Hirudins
Serum-Free Culture Media
Warfarin
Growth
Sarcoma
Endothelium
Endothelial Cells
Cell Line

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Zhang, Y., Deng, Y., Luther, T., Müller, M., Ziegler, R., Waldherr, R., ... Nawroth, P. P. (1994). Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice. Journal of Clinical Investigation, 94(3), 1320-1327. https://doi.org/10.1172/JCI117451

Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice. / Zhang, Youming; Deng, Youhua; Luther, Thomas; Müller, Martin; Ziegler, Reinhard; Waldherr, Rüdiger; Stern, David; Nawroth, Peter Paul.

In: Journal of Clinical Investigation, Vol. 94, No. 3, 01.01.1994, p. 1320-1327.

Research output: Contribution to journalArticle

Zhang, Y, Deng, Y, Luther, T, Müller, M, Ziegler, R, Waldherr, R, Stern, D & Nawroth, PP 1994, 'Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice', Journal of Clinical Investigation, vol. 94, no. 3, pp. 1320-1327. https://doi.org/10.1172/JCI117451
Zhang, Youming ; Deng, Youhua ; Luther, Thomas ; Müller, Martin ; Ziegler, Reinhard ; Waldherr, Rüdiger ; Stern, David ; Nawroth, Peter Paul. / Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice. In: Journal of Clinical Investigation. 1994 ; Vol. 94, No. 3. pp. 1320-1327.
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