Role of tissue factor expression on tumour cell invasion and growth of experimental pancreatic adenocarcinoma
Role of tissue factor expression on tumour cell invasion and growth of experimental pancreatic adenocarcinoma
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DOI:
10.1046/j.1365-2168.1999.01153.x
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发表时间:
1999-07-01
影响因子:
9.6
通讯作者:
Williamson, RCN
中科院分区:
文献类型:
--
作者:
Kakkar, AK;Chinswangwatanakul, V;Williamson, RCN
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) iras 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 lit vitro invasion and primary tumour growth of MIAPaCa-2 cells, suggesting that this procoagulant molecule might have a role in pancreatic tumour biology.