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

Clin Exp Metastasis. 2002;19(2):181-9. doi: 10.1023/a:1014598904644.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology*
  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Differentiation*
  • DNA Primers / chemistry
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology*
  • RNA, Messenger / metabolism
  • Receptor, PAR-1
  • Receptors, Thrombin / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • DNA Primers
  • RNA, Messenger
  • Receptor, PAR-1
  • Receptors, Thrombin