title: Pancreatic cancer cell and microparticle procoagulant surface characterization:  involvement of membrane-expressed tissue factor, phosphatidylserine and phosphatidylethanolamine.
abstract: 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.
authors.affiliation: Postgraduate Medical Institute, University of Hull, Hull, UK.
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Yates
authors.forename: Jessica
authors.initials: J
authors.lastname: Welsh
authors.forename: Hussein H
authors.initials: HH
authors.lastname: Echrish
authors.forename: John
authors.initials: J
authors.lastname: Greenman
authors.forename: Anthony
authors.initials: A
authors.lastname: Maraveyas
authors.forename: Leigh A
authors.initials: LA
authors.lastname: Madden
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D001430:Bacteriocins / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D002277:Carcinoma / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D055252:Cell-Derived Microparticles / Q000737:chemistry*; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry; D011517:Prothrombin Time; D013917:Thrombin / Q000032:analysis / Q000096:biosynthesis; D013925:Thromboplastin / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D054556:Venous Thromboembolism / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
chemical_list: D001430:Bacteriocins; D017077:Culture Media, Conditioned; D010455:Peptides; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; C040522:duramycin; C483858:phosphatidylethanolamine; D013925:Thromboplastin; D013917:Thrombin