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
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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.
Blood 04/2012; 119(23):5543-52. · 9.90 Impact Factor
