Role of tissue factor expression on tumour cell invasion and growth of experimental pancreatic adenocarcinoma

Abstract

Abstract 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. Conclusion 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.