PAR 1-type thrombin receptors are involved in thrombin-induced calcium signaling in human meningioma cells

J Neurooncol. 1999 Apr;42(2):131-6. doi: 10.1023/a:1006246219449.

Abstract

Thrombin is known to play a role as regulator in tumor spreading and tumor growth. Proteinase-activated receptor 1 (PAR 1)-type thrombin receptors were identified in different cancer cells including human glioblastoma cells. Thus a function of PAR 1 in brain tumors may be suggested. In this study, the presence of PAR 1-type thrombin receptors was investigated in primary cell cultures established from operated human meningiomas from two 59- and 79-year-old women. Characterization of PAR 1 on binding level was performed using immunofluorescence studies with the monoclonal anti-PAR 1 antibody Mab 61-1 directed against a domain in the NH2-terminus of PAR 1. These binding sites constitute functional thrombin receptors that are involved in thrombin-induced signaling in human meningioma cells as demonstrated by investigation of alpha-thrombin- and PAR 1-activating hexapeptide (TRAP-6)-induced [Ca2+]i mobilization. To our knowledge, this is the first report demonstrating thrombin-induced intracellular signaling in human meningioma cells mediated by the PAR 1-type thrombin receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amino Acid Sequence
  • Calcium / metabolism*
  • Female
  • Humans
  • Meningeal Neoplasms / metabolism
  • Meningeal Neoplasms / pathology
  • Meningeal Neoplasms / physiopathology*
  • Meningioma / metabolism
  • Meningioma / pathology
  • Meningioma / physiopathology*
  • Middle Aged
  • Molecular Sequence Data
  • Peptide Fragments / pharmacology
  • Receptor, PAR-1
  • Receptors, Thrombin / physiology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Thrombin / pharmacology
  • Thrombin / physiology*
  • Tumor Cells, Cultured

Substances

  • Peptide Fragments
  • Receptor, PAR-1
  • Receptors, Thrombin
  • thrombin receptor peptide (42-47)
  • Thrombin
  • Calcium