Basic Research
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World J Gastroenterol. Aug 14, 2006; 12(30): 4843-4849
Published online Aug 14, 2006. doi: 10.3748/wjg.v12.i30.4843
Expression of tissue factor in pancreatic adenocarcinoma is associated with activation of coagulation
Stephan L Haas, Ralf Jesnowski, Michael Steiner, Frank Hummel, Jörg Ringel, Christine Burstein, Horst Nizze, Stefan Liebe, J Matthias Löhr
Stephan L Haas, Ralf Jesnowski, Frank Hummel, Jörg Ringel, J Matthias Löhr, Department of Medicine II, University of Heidelberg at Mannheim, Germany
Michael Steiner, Christine Burstein, Department of Clinical Chemistry and Pathobiochemistry, University of Rostock, Rostock, Germany
Horst Nizze, Department of Pathology, University of Rostock, Rostock, Germany
Stefan Liebe, Department of Medicine, University of Rostock, Rostock, Germany
Author contributions: All authors contributed equally to the work.
Supported by the Ministry of Science, State of Mecklenburg; Grant No. RVFF UR40 to J Matthias Löhr and Dr. Robert-Pfleger Stiftung to J Matthias Löhr, Bamberg, Germany
Correspondence to: J Matthias Löhr, MD, Molecular Gastroenterology Unit (DKFZ E180), Department of Medicine II, University of Heidelberg at Mannheim, Theodor-Kutzer Ufer 1-3, D-68167 Mannheim, Germany. matthias.loehr@med.ma.uni-heidelberg.de
Telephone: +49-621-3832090 Fax: +49-621-3831986
Received: August 23, 2005
Revised: October 1, 2005
Accepted: October 10, 2005
Published online: August 14, 2006
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: Coagulation activation; Pancreatic carcinoma; Thromboembolism; Thrombosis; Tissue factor