Journal
BRITISH JOURNAL OF CANCER
Volume 101, Issue 12, Pages 2023-2029Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6605406
Keywords
coagulation factor VII; tissue factor; hypoxia; ovarian cancer; TF-positive microparticle
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Funding
- Grant-in-Aid for the Encouragement of Basic Science and Technology from the Science and Technology Office of the Kanagawa Prefectural Government
- Japanese Ministry of Education, Culture, Sports, Science and Technology
- Grants-in-Aid for Scientific Research [23501280] Funding Source: KAKEN
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BACKGROUND: Thromboembolic events are a major complication in ovarian cancer patients. Tissue factor (TF) is frequently overexpressed in ovarian cancer tissue and correlates with intravascular thrombosis. TF binds to coagulation factor VII (fVII), changing it to its active form, fVIIa. This leads to activation of the extrinsic coagulation cascade. fVII is produced by the liver and believed to be supplied from blood plasma at the site of coagulation. However, we recently showed that ovarian cancer cells express fVII transcripts under normoxia and that this transcription is inducible under hypoxia. These findings led us to hypothesise that ovarian cancer cells are intrinsically associated with TF-fVIIa coagulation activity, which could result in thrombosis. METHODS: In this study, we examined whether ectopically expressed fVII could cause thrombosis by means of immunohistochemistry, RT-PCR, western blotting and flow cytometry. RESULTS: Ectopic fVII expression occurs frequently in ovarian cancers, particularly in clear cell carcinoma. We further showed that ovarian cancer cells express TF-fVIIa on the cell surface under normoxia and that this procoagulant activity is enhanced by hypoxic stimuli. Moreover, we showed that ovarian cancer cells secrete microparticles (MPs) with TF-fVIIa activity. Production of this procoagulant secretion is enhanced under hypoxia. CONCLUSION: These results raise the possibility that cancer cell-derived TF-fVIIa could cause thrombotic events in ovarian cancer patients. British Journal of Cancer (2009) 101, 2023-2029. doi: 10.1038/sj.bjc.6605406 www.bjcancer.com Published online 10 November 2009 (C) 2009 Cancer Research UK
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