Expression of the thrombin receptor PAR-1 correlates with tumour cell differentiation of pancreatic adenocarcinoma in vitro

Expression of the thrombin receptor PAR-1 correlates with tumour cell differentiation of pancreatic adenocarcinoma in vitro
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凝血酶受体 PAR-1 的表达与体外胰腺腺癌的肿瘤细胞分化相关

DOI:
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发表时间:
2004
影响因子:
4
通讯作者:
E. Neugebauer
E. Neugebauer
中科院分区:
医学3区
文献类型:
--
作者:
C. Rudroff;S. Seibold;R. Kaufmann;Cecilia Cu Zetina;Kathrin Reise;U. Schäfer;A. Schneider;M. Brockmann;J. Scheele;E. Neugebauer

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胰腺癌患者常因凝血酶生成过多而形成血栓。然而,凝血酶对胰腺癌的作用仍然知之甚少。凝血酶受体PAR-1负责凝血酶的细胞效应。PAR-1在体外不同实体肿瘤的进展中起重要作用。在乳腺癌中,PAR-1的表达水平与浸润性相关。我们的目的是将PAR-1 mRNA和蛋白表达水平与胰腺组织和癌细胞的分化程度联系起来。正常胰腺上皮未检出PAR-1蛋白。免疫荧光染色法分析胰腺癌细胞系中PAR-1蛋白的表达与分化程度相关。Western Blot定量分析PAR-1蛋白表达证实了这些观察结果。PAR-1 mRNA表达分析显示,与胰腺癌组织和胰腺癌细胞系MIA PaCa-2相比,健康胰腺中的PAR-1 mRNA表达水平较低。PAR-1 mRNA的水平在不同的胰腺癌细胞系之间差异高达25倍。在体内和体外健康胰腺组织和胰腺癌中,PAR-1蛋白和mRNA表达的显著差异强调了PAR-1在胰腺癌进展中的假定作用。
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.
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