Expression of tissue factor in pancreatic adenocarcinoma is associated with activation of coagulation.
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.
Haas
Stephan L
SL
Department of Medicine II, University of Heidelberg at Mannheim, D-68167 Mannheim, Germany.
Jesnowski
Ralf
R
Steiner
Michael
M
Hummel
Frank
F
Ringel
Jörg
J
Burstein
Christine
C
Nizze
Horst
H
Liebe
Stefan
S
Löhr
J Matthias
JM
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*
D013925:Thromboplastin