Tumor-derived tissue factor activates coagulation and enhances thrombosis in a mouse xenograft model of human pancreatic cancer
Open Access
- 7 June 2012
- journal article
- Published by American Society of Hematology in Blood
- Vol. 119 (23), 5543-5552
- https://doi.org/10.1182/blood-2012-01-402156
Abstract
Cancer patients often have an activated clotting system and are at increased risk for venous thrombosis. In the present study, we analyzed tissue factor (TF) expression in 4 different human pancreatic tumor cell lines for the purpose of producing derivative tumors in vivo. We found that 2 of the lines expressed TF and released TF-positive microparticles (MPs) into the culture medium. The majority of TF protein in the culture medium was associated with MPs. Only TF-positive cell lines activated coagulation in nude mice, and this activation was abolished by an anti–human TF Ab. Of the 2 TF-positive lines, only one produced detectable levels of human MP TF activity in the plasma when grown orthotopically in nude mice. Surprisingly, < 5% of human TF protein in plasma from tumor-bearing mice was associated with MPs. Mice with TF-positive tumors and elevated levels of circulating TF-positive MPs had increased thrombosis in a saphenous vein model. In contrast, we observed no difference in thrombus weight between tumor-bearing and control mice in an inferior vena cava stenosis model. The results of the present study using a xenograft mouse model suggest that tumor TF activates coagulation, whereas TF on circulating MPs may trigger venous thrombosis.Keywords
This publication has 42 references indexed in Scilit:
- Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivoThe Journal of Experimental Medicine, 2012
- Pre-analytical and analytical variables affecting the measurement of plasma-derived microparticle tissue factor activityThrombosis Research, 2012
- Overexpression of the Cell Cycle Inhibitor p16 INK4a Promotes a Prothrombotic Phenotype Following Vascular Injury in MiceArteriosclerosis, Thrombosis, and Vascular Biology, 2011
- Increased microparticle tissue factor activity in cancer patients with Venous ThromboembolismThrombosis Research, 2010
- Tumor-Derived Tissue FactorBearing Microparticles Are Associated With Venous Thromboembolic Events in MalignancyClinical Cancer Research, 2009
- Cancer cell–derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivoThe Journal of Experimental Medicine, 2009
- Levels of microparticle tissue factor activity correlate with coagulation activation in endotoxemic miceJournal of Thrombosis and Haemostasis, 2009
- Mucin Glycosylation Is Altered by Pro-Inflammatory Signaling in Pancreatic-Cancer CellsJournal of Proteome Research, 2009
- Plasma tissue factor may be predictive of venous thromboembolism in pancreatic cancerJournal of Thrombosis and Haemostasis, 2008
- Microparticle‐associated tissue factor activity: a link between cancer and thrombosis?Journal of Thrombosis and Haemostasis, 2007