Rudroff Claudia, Seibold Stefan, Kaufmann Roland, Zetina Cecilia Cu, Reise Kathrin, Schäfer Ute, Schneider Annette, Brockmann Michael, Scheele Johannes, Neugebauer Edmund A M
Second Department of Surgery, University of Cologne, Germany.
Clin Exp Metastasis. 2002;19(2):181-9. doi: 10.1023/a:1014598904644.
Patients with pancreatic cancer frequently suffer from thrombosis due to excess thrombin generation. Yet, the effects of thrombin on pancreatic cancer are still poorly understood. The thrombin receptor PAR-1 is responsible for cellular effects of thrombin. PAR-1 plays an important role in the progression of different solid tumours in vitro. In breast cancer the level of PAR-1 expression correlates with invasiveness. Our aim was to correlate PAR-1 mRNA and protein expression level with the grade of differentiation of pancreatic tissue and cancer cell lines. PAR-1 protein was not detectable in the epithelium of healthy pancreas. Analysis of PAR-1 protein expression by immunofluorescence staining of pancreatic cancer cell lines revealed a correlation to the grade of differentiation. Quantitative analysis of PAR-1 protein expression by Western Blot analysis confirmed these observations. Analysis of PAR-1 mRNA expression showed low levels in healthy pancreas compared to pancreatic cancer tissue and the pancreatic cancer cell line MIA PaCa-2. The level of PAR-1 mRNA differed up to 25 fold between the respective pancreatic cancer cell lines. The eminent differences in PAR-1 expression, both protein and mRNA, between healthy pancreatic tissue and pancreatic cancer in vivo and in vitro emphasise the putative role of PAR-1 in pancreatic cancer progression.
胰腺癌患者常因凝血酶生成过多而发生血栓形成。然而，凝血酶对胰腺癌的影响仍知之甚少。凝血酶受体PAR-1介导凝血酶的细胞效应。PAR-1在不同实体瘤的体外进展中起重要作用。在乳腺癌中，PAR-1的表达水平与侵袭性相关。我们的目的是将PAR-1 mRNA和蛋白表达水平与胰腺组织及癌细胞系的分化程度相关联。在健康胰腺的上皮中未检测到PAR-1蛋白。通过对胰腺癌细胞系进行免疫荧光染色分析PAR-1蛋白表达，发现其与分化程度相关。通过蛋白质印迹分析对PAR-1蛋白表达进行定量分析证实了这些观察结果。与胰腺癌组织及胰腺癌细胞系MIA PaCa-2相比，健康胰腺中PAR-1 mRNA表达水平较低。各胰腺癌细胞系之间PAR-1 mRNA水平差异高达25倍。健康胰腺组织与体内外胰腺癌之间PAR-1在蛋白和mRNA表达上的显著差异，强调了PAR-1在胰腺癌进展中的假定作用。
