PAR 1-type thrombin receptors are involved in thrombin-induced calcium signaling in human meningioma cells.
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.
Research Unit Pharmacological Hemostaseology, Friedrich Schiller University Jena, Germany. rol@leech.mpg.uni-jena-de
R
R
Kaufmann
S
S
Patt
R
R
Kraft
M
M
Zieger
P
P
Henklein
G
G
Neupert
G
G
Nowak
D000368:Aged; D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism*; D005260:Female; D006801:Humans; D008577:Meningeal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008579:Meningioma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013917:Thrombin / Q000494:pharmacology / Q000502:physiology*; D014407:Tumor Cells, Cultured
D010446:Peptide Fragments; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; C082835:thrombin receptor peptide (42-47); D013917:Thrombin; D002118:Calcium