Neurotensin promotes the progression of malignant glioma through NTSR1 and impacts the prognosis of glioma patients

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• 作者：Qing Ouyang (1) (2)
  Xueyang Gong (2)
  Hualiang Xiao (4)
  Ji Zhou (1)
  Minhui Xu (1)
  Yun Dai (5)
  Lunshan Xu (1)
  Hua Feng (3)
  Hongjuan Cui (2)
  Liang Yi (1)
  
  1. Department of Neurosurgery ; Daping Hospital ; Third Military Medical University ; Chongqing ; China
  2. State Key Laboratory of Silkworm Genome Biology ; Institute of Sericulture and Systems Biology ; Southwest University ; Chongqing ; China
  4. Department of Pathology ; Daping Hospital ; Third Military Medical University ; Chongqing ; China
  5. Division of Hematology/Oncology ; Department of Medicine ; Virginia Commonwealth University ; Richmond ; VA ; USA
  3. Department of Neurosurgery ; Southwest Hospital ; Third Military Medical University ; Chongqing ; China
  
• 关键词：Glioma ; Neurotensin ; Proliferation ; Invasion
• 刊名：Molecular Cancer
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：14
• 期：1
• 全文大小：1,676 KB
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• 刊物主题：Cancer Research; Oncology;
• 出版者：BioMed Central
• ISSN：1476-4598

文摘

Background 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. Methods NTS 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. Results Positive 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. Conclusion NTS 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.