Abstract
BackgroundThe poor prognosis and minimally successful treatments of malignant glioma indicate a challenge to identify new therapeutic targets which impact glioma progression. Neurotensin (NTS) and its high affinity receptor (NTSR1) overexpression induces neoplastic growth and predicts the poor prognosis in various malignancies. Whether NTS can promote the glioma progression and its prognostic significance for glioma patients remains unclear.MethodsNTS precursor (ProNTS), NTS and NTSR1 expression levels in glioma were detected by immunobloting Elisa and immunohistochemistry assay. The prognostic analysis was conducted from internet by R2 microarray platform. Glioma cell proliferation was evaluated by CCK8 and BrdU incorporation assay. Wound healing model and Matrigel transwell assay were utilized to test cellular migration and invasion. The orthotopic glioma implantations were established to analyze the role of NTS and NTSR1 in glioma progression in vivo.ResultsPositive correlations were shown between the expression levels of NTS and NTSR1 with the pathological grade of gliomas. The high expression levels of NTS and NTSR1 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. NTS stimulated Erk1/2 phosphorylation in glioma cells, which could be reversed by SR48692 or NTSR1-siRNA. In vivo experiments showed that SR48692 significantly prolonged the survival length of glioma-bearing mice and inhibited glioma cell invasiveness.ConclusionNTS promotes the proliferation and invasion of glioma via the activation of NTSR1. High expression levels of NTS and NTSR1 predict a poor prognosis in glioma patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-015-0290-8) contains supplementary material, which is available to authorized users.
Highlights
The poor prognosis and minimally successful treatments of malignant glioma indicate a challenge to identify new therapeutic targets which impact glioma progression
We firstly reported that high levels of NTS or neurotensin receptor 1 (NTSR1) expression were correlated with a poor prognosis in the glioma patient, which would be a potential target for glioma treatment and need to be further investigated
The NTS/NTSR1 were detected by immunohistochemistry (IHC) and the results confirmed that NTS/NTSR1 expression were obviously elevated in human glioma compared with the peritumoral tissue and the relative normal brain tissue (Figure 1A)
Summary
The poor prognosis and minimally successful treatments of malignant glioma indicate a challenge to identify new therapeutic targets which impact glioma progression. Neurotensin (NTS) and its high affinity receptor (NTSR1) overexpression induces neoplastic growth and predicts the poor prognosis in various malignancies. Whether NTS can promote the glioma progression and its prognostic significance for glioma patients remains unclear. NTS is mainly secreted by endocrine N-cells of the gastrointestinal tract and plays the role of a neurocrine hormone to regulate the postprandial digestive process. It inhibits gut motility and gastric acid secretions, stimulates the pancreatic and biliary secretions and improves the fatty acid ingestion [5,6]
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