P01.23 * NEUROTENSIN PROMOTES THE PROGRESSION OF MALIGNANT GLIOMA THROUGH NTSR1 AND IMPACTS THE PROGNOSIS OF GLIOMA PATIENTS

Abstract

BACKGROUND: Neurotensin (NTS) functions as a neuromodulator and induces cellular proliferation and migration in various solid tumors. However, whether NTS can promote the progression of malignant glioma and its prognostic significance for glioma patients remain unclear. METHODS: NTS and its high-affinity receptor (NTSR1) expression levels in clinical glioma samples were detected by immunohistochemistry and immunobloting. The prognostic analysis in glioma patients were conducted online by R2 microarray analysis and the visualization platform. The proliferation of glioma cells were evaluated by CCK8 and BrdU incorporation assay. The celluar invasiveness were tested by wound healing model and the Matrigel transwell assay. A neutralizing antibody to NTS, NTSR1-selective antagonist SR48692 and NTSR1-siRNA were used to suppress the NTS stimulation. Erk1/2 phosphorylation was tested by immunobloting. The orthotopic glioma implantation model was established to examine the role of NTS and NTSR1 in the progression of glioma in vivo. RESULTS: Positive correlations were shown between the expression levels of NTS and NTSR1 with the pathological grade of gliomas. The high levels of NTS and NTSR1 expression indicate a worse prognosis in glioma patients. The proliferation and invasiveness of glioma cells could be enhanced by NTS stimulation and impaired by the inhibition of NTSR1 functions. NTS stimulated Erk1/2 phosphorylation in glioma cells, which could be reversed by treatment with SR48692 or NTSR1-siRNA. In vivo experiments showed that therapy with SR48692 significantly prolonged the survival length of glioma-bearing mice and inhibited glioma cell invasiveness in vivo. CONCLUSIONS: NTS promotes the proliferation and invasion of glioma via the activation of NTSR1 and its downstream signaling molecules, resulting in Erk1/2 phosphorylation. High levels of NTS and NTSR1 expression predict a bad prognosis in glioma patients.