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Pancreatic cancer cell and microparticle procoagulant surface characterization: involvement of membrane-expressed tissue factor, phosphatidylserine and phosphatidylethanolamine

Yates, Katherine R.a,*; Welsh, Jessicaa,*; Echrish, Hussein H.a; Greenman, Johna; Maraveyas, Anthonyb; Madden, Leigh A.a

Blood Coagulation & Fibrinolysis: December 2011 - Volume 22 - Issue 8 - p 680–687
doi: 10.1097/MBC.0b013e32834ad7bc
ORIGINAL ARTICLES

Advanced pancreatic cancer is associated with a high risk of patients developing venous thromboembolism. This increased risk is thought to be tumour-driven and associated with tissue factor (TF) and microparticles. The aim of this study was to investigate the role of TF and phospholipid expression in the procoagulant properties of pancreatic cell lines and microparticles. Pancreatic cancer cell lines (MIA-PaCa-2, ASPC-1 and CFPAC-1) were assessed for expression of TF and microparticle release. Procoagulant potential was determined by a prothrombin time assay. Cell surface expression of TF was highest in CFPAC-1, with low expression on ASPC-1 and little/no expression on MIA-PaCa-2. Clotting time (CT) was cell number and TF-dependent (P < 0.001). Blocking of TF resulted in slower CT for CFPAC-1 and ASPC1 and prevented clotting in MIA-PaCa-2. Microparticles were shown to be procoagulant and the majority of procoagulant potential could be removed by passing cell-free media through a 0.1 μm filter. A dose-dependent CT was observed in both ASPC-1 and CFPAC-1 cell-free media. Furthermore, addition of duramycin prevented microparticle-supported coagulation. The data presented suggest a key role for cell and microparticle surface-expressed TF and phospholipids in coagulation and highlight duramycin-mediated disruption of clotting.

aPostgraduate Medical Institute, University of Hull, Hull

bQueen's Centre for Oncology and Haematology, Castle Hill Hospital, Cottingham, UK

Correspondence to Leigh A. Madden, Room 003, Hardy Building, University of Hull, Hull HU6 7RX, UK Tel: +44 1482 466031; fax: +44 1482 466031; e-mail: l.a.madden@hull.ac.uk

* Katherine R. Yates and Jessica Welsh contributed equally to the writing of the article.

Received 18 March, 2011

Revised 4 July, 2011

Accepted 9 July, 2011

© 2011 Lippincott Williams & Wilkins, Inc.