This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 23/5/905    most recent 01.ATV.0000067700.77438.3Fv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Philipp, J. Articles by Gottstein, C. Search for Related Content PubMed PubMed Citation Articles by Philipp, J. Articles by Gottstein, C. Related Collections Coagulation Thrombosis risk factors Coagulation and fibronolysis

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:905.)
© 2003 American Heart Association, Inc.

Thrombosis

Soluble Tissue Factor Induces Coagulation on Tumor Endothelial Cells In Vivo if Coadministered With Low-Dose Lipopolysaccharides

Jana Philipp; Ariane Dienst; Maike Unruh; Anke Wagener; Andrea Grunow; Andreas Engert; Jochen W.U. Fries; Claudia Gottstein

From the Department of Internal Medicine I and the Department of Pathology (J.W.U.F.), University Hospital Cologne, Cologne, Germany.

Correspondence to Claudia Gottstein, MD, University Hospital Cologne, Department of Internal Medicine I, Laboratory for Tumor Therapy, LFI E4 R707, Joseph-Stelzmann-Str. 9, 50924 Cologne, Germany. E-mail claudia.gottstein{at}uni-koeln.de

Objective— This study was performed to evaluate the mechanisms leading to tumor vessel occlusion by tissue factor–based drugs, which are used in vascular targeting approaches for the treatment of malignant tumors.

Methods and Results— The effects of nontargeted soluble tissue factor were evaluated in vitro and in vivo. Tumor-bearing mice were treated with (1) the extracellular portion of tissue factor (soluble tissue factor), (2) low nontoxic doses of lipopolysaccharides, or (3) a combination thereof. The combination treatment showed the best effects and resulted in selective thrombosis of tumor vessels. On the basis of our data from subsequent in vitro analyses, including surface plasmon resonance measurements and endothelial cell based coagulation assays, we propose a model on how soluble tissue factor, although lacking its membrane anchor, can promote selective tumor vessel occlusion.

Conclusions— To our knowledge, this is the first report to describe the molecular mechanisms of coagulation induction by untargeted soluble tissue factor in vivo. Combination treatments including soluble tissue factor might represent an alternative vascular targeting approach for the treatment of malignant tumors.

Key Words: soluble tissue factor • tumor endothelium • lipopolysaccharides • coagulation • vascular targeting

This article has been cited by other articles:

				K. Yoshizawa, G. E. Kissling, J. A. Johnson, N. P. Clayton, N. D. Flagler, and A. Nyska Chemical-Induced Atrial Thrombosis in NTP Rodent Studies Toxicol Pathol, August 1, 2005; 33(5): 517 - 532. [Abstract] [Full Text] [PDF]

				M. Guba, M. Yezhelyev, M. E. Eichhorn, G. Schmid, I. Ischenko, A. Papyan, C. Graeb, H. Seeliger, E. K. Geissler, K.-W. Jauch, et al. Rapamycin induces tumor-specific thrombosis via tissue factor in the presence of VEGF Blood, June 1, 2005; 105(11): 4463 - 4469. [Abstract] [Full Text] [PDF]

				A. Dienst, A. Grunow, M. Unruh, B. Rabausch, J. E. Nor, J. W. U. Fries, and C. Gottstein Specific Occlusion of Murine and Human Tumor Vasculature by VCAM-1-Targeted Recombinant Fusion Proteins J Natl Cancer Inst, May 18, 2005; 97(10): 733 - 747. [Abstract] [Full Text] [PDF]