Higher expression of PAR-1 may be associated with severity of Glioblastomas

Abstract Glioblastoma multiforme (GBM) is one of the most malignant types of central nervous system tumors. Protease-activated receptor 1 (PAR1) is a G protein-coupled receptor that elicits several pro-tumoral responses. It has been linked to proliferation and invasiveness in glioblastomas. In the present study, prevalence of the receptor (PAR-1) and its associated downstream signaling was studied in two human glioblastoma cell lines D-54 MG and U-87 MG. The expression of PAR1 was found to be significantly higher in D-54 MG cell-line when compared to U-87 MG cell-line. The activation of PAR-1 in the presence of TFLLR (a synthetic peptide activator of PAR-1) led to an increase in ERK ½ activity along with a significant increase in the migration and invasion of these cell-lines. Subsequent treatment with SCH-79797 (PAR-1 inhibitor) significantly decreased the migration and invasion in these glioma cell lines, respectively. The relative increase and decrease in the migration and invasion of these cell lines in presence of activator and inhibitor respectively was found to be linked with the expression of PAR-1. To conclude the study links the PAR-1 signaling with progression of Glioblastoma. PAR-1 and associated downstream signaling may be a potential therapeutic target to preclude the pathogenesis of gliomas.