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.
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Authors | Jian-Guo Wang, Julia E Geddings, Maria M Aleman, Jessica C Cardenas, Pichika Chantrathammachart, Julie C Williams, Daniel Kirchhofer, Vladimir Y Bogdanov, Ronald R Bach, Janusz Rak, Frank C Church, Alisa S Wolberg, Rafal Pawlinski, Nigel S Key, Jen Jen Yeh, Nigel Mackman |
Journal | Blood
(Blood)
Vol. 119
Issue 23
Pg. 5543-52
(Jun 07 2012)
ISSN: 1528-0020 [Electronic] United States |
PMID | 22547577
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- RNA, Messenger
- Thromboplastin
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Topics |
- Animals
- Blood Coagulation
- Cell Line, Tumor
- Cell-Derived Microparticles
(metabolism)
- Colorectal Neoplasms
(genetics, metabolism)
- Gene Expression Regulation, Neoplastic
- Hemostasis
- Humans
- Mice
- Mice, Nude
- Pancreatic Neoplasms
(complications, genetics, metabolism)
- RNA, Messenger
(genetics)
- Thromboplastin
(genetics, metabolism)
- Venous Thrombosis
(complications, metabolism)
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