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

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 MIAPaCa-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 MIAPaCa-2 cells, suggesting that this procoagulant molecule might have a role in pancreatic tumour biology.