Role of tissue factor expression on tumour cell invasion and growth of experimental pancreatic adenocarcinoma.
BACKGROUND
Tissue factor (TF), the physiological procoagulant, is expressed in pancreatic tissue as a result of malignant transformation. The aim of this investigation was to assess its role in pancreatic tumour cell invasion and primary tumour growth.


METHODS
The full-length TF gene (1360 base pairs) was cloned into the plasmid DNA vector pcDNA3 in sense and antisense orientations, and these vectors were used to transfect the MIA PaCa-2 human pancreatic adenocarcinoma cell line. TF gene expression was characterized by Northern blot analysis, total cellular antigenic content by enzyme-linked immunosorbent assay and cell surface procoagulant activity by enzymatic assay. Invasion of tumour cells in vitro was determined by a standard Matrigel assay, and primary tumour growth was measured in immunodeficient mice.


RESULTS
Overexpression of the TF gene, confirmed by an increased signal on Northern blotting, was associated with increases in both total antigenic content for TF (P = 0.001) and cell surface procoagulant activity (P = 0.008) in sense cells compared with wild-type cells. Likewise, both in vitro tumour cell invasion (P = 0.001) and primary tumour growth (P = 0.007) were increased in sense transfectants.


CONCLUSIONS
Expression of TF enhances in vitro invasion and primary tumour growth of MIA PaCa-2 cells, suggesting that this procoagulant molecule might have a role in pancreatic tumour biology. Presented in part to the 83rd meeting of the Surgical Research Society, Oxford, UK, January 1996 and awarded the David Patey Prize, and in part to the 1997 Annual Meeting of the Association of Surgeons of Great Britain and Ireland, Bournemouth, UK, April 1997.
Department of Surgery, Imperial College School of Medicine, London, UK.
A K
AK
Kakkar
V
V
Chinswangwatanakul
N R
NR
Lemoine
S
S
Tebbutt
R C
RC
Williamson
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division; D005260:Female; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D013925:Thromboplastin / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D013925:Thromboplastin