Kakkar A K, Chinswangwatanakul V, Lemoine N R, Tebbutt S, Williamson R C
Department of Surgery, Imperial College School of Medicine, London, UK.
Br J Surg. 1999 Jul;86(7):890-4. doi: 10.1046/j.1365-2168.1999.01153.x.
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.
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.
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.
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.
组织因子（TF）是一种生理性促凝剂，在胰腺组织中因恶性转化而表达。本研究的目的是评估其在胰腺肿瘤细胞侵袭和原发性肿瘤生长中的作用。
将全长TF基因（1360个碱基对）以正义和反义方向克隆到质粒DNA载体pcDNA3中，并用这些载体转染MIA PaCa-2人胰腺腺癌细胞系。通过Northern印迹分析表征TF基因表达，通过酶联免疫吸附测定法测定总细胞抗原含量，通过酶促测定法测定细胞表面促凝活性。体外肿瘤细胞侵袭通过标准基质胶测定法确定，原发性肿瘤生长在免疫缺陷小鼠中进行测量。
与野生型细胞相比，通过Northern印迹上信号增加证实的TF基因过表达与正义细胞中TF的总抗原含量增加（P = 0.001）和细胞表面促凝活性增加（P = 0.008）相关。同样，正义转染子中体外肿瘤细胞侵袭（P = 0.001）和原发性肿瘤生长（P = 0.007）均增加。
TF的表达增强了MIA PaCa-2细胞的体外侵袭和原发性肿瘤生长，表明这种促凝分子可能在胰腺肿瘤生物学中起作用。部分内容于1996年1月在英国牛津举行的外科研究学会第83次会议上发表，并获得大卫·佩蒂奖，部分内容于1997年4月在英国伯恩茅斯举行的大不列颠及爱尔兰外科医生协会1997年年会发表。
