title: Expression of tissue factor in pancreatic adenocarcinoma is associated with activation of coagulation.
abstract: OBJECTIVE
  To study expression of tissue factor (TF) in pancreatic cancer and its role in the development of thromboembolism.
  
  
  METHODS
  TF expression was studied in eight human pancreatic carcinoma cell lines by Northern blot and indirect immunofluorescence. Expression of alternatively spliced TF (asTF) was assessed by RT-PCR. In addition, TF expression was determined by immunofluorescence in pancreatic tissues of 19 patients with pancreatic adenocarcinoma (PCa), 9 patients with chronic pancreatitis (CP) and 20 normal controls. Plasma samples (30 PCa-patients, 13 CP-patients and 20 controls) were investigated for soluble TF levels and coagulation activation markers [thrombin-antithrombin III complex (TAT), prothrombin fragment 1 + 2 (F1 + 2)].
  
  
  RESULTS
  All pancreatic carcinoma cell lines expressed TF (8/8) and most of them expressed asTF (6/8). TF expression at the protein level did not correlate with the differentiation of the carcinoma cell line. All but two pancreatic cancer tissue samples stained positive for TF (17/19). In all samples of CP weak staining was restricted to pancreatic duct cells, whereas only a few subendothelial cells were positive in 9/20 of normal controls. TF and TAT levels in PCa patients were significantly elevated compared to controls whereas elevated F1 + 2 levels did not reach statistical significance compared to controls. In CP patients TAT and F1 + 2 levels proved to be significantly elevated compared to controls, although TAT elevation was less pronounced than in PCa patients.
  
  
  CONCLUSIONS
  We conclude that in addition to the upregulated expression of TF on the cell membrane, soluble TF might contribute to activation of the coagulation system in pancreatic cancer.
authors.affiliation: Department of Medicine II, University of Heidelberg at Mannheim, D-68167 Mannheim, Germany.
authors.forename: Stephan L
authors.initials: SL
authors.lastname: Haas
authors.forename: Ralf
authors.initials: R
authors.lastname: Jesnowski
authors.forename: Michael
authors.initials: M
authors.lastname: Steiner
authors.forename: Frank
authors.initials: F
authors.lastname: Hummel
authors.forename: Jörg
authors.initials: J
authors.lastname: Ringel
authors.forename: Christine
authors.initials: C
authors.lastname: Burstein
authors.forename: Horst
authors.initials: H
authors.lastname: Nizze
authors.forename: Stefan
authors.initials: S
authors.lastname: Liebe
authors.forename: J Matthias
authors.initials: JM
authors.lastname: Löhr
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000378:metabolism*; D000368:Aged; D001777:Blood Coagulation; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000150:complications / Q000378:metabolism*; D013923:Thromboembolism / Q000209:etiology / Q000378:metabolism*; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*
chemical_list: D013925:Thromboplastin