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

Abstract

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.