Neurotensin promotes the progression of malignant glioma through NTSR1 and impacts the prognosis of glioma patients.
Neurotensin promotes the progression of malignant glioma through NTSR1 and impacts the prognosis of glioma patients.
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神经降压素通过NTSR1促进恶性胶质瘤的进展并影响胶质瘤患者的预后。
DOI：
10.1186/s12943-015-0290-8
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发表时间：
2015-02-03
期刊：
影响因子：
37.3
通讯作者：
Yi L
中科院分区：
文献类型：
--
作者：
Ouyang Q;Gong X;Xiao H;Zhou J;Xu M;Dai Y;Xu L;Feng H;Cui H;Yi L
恶性胶质瘤的预后差和最小成功的治疗表明了确定影响胶质瘤进展的新治疗靶点的挑战。神经降压素（NTS）及其高亲和力受体（NTSR 1）的过度表达诱导肿瘤生长，并预测各种恶性肿瘤的不良预后。NTS是否能促进胶质瘤的进展及其对胶质瘤患者预后的意义尚不清楚。采用免疫印迹法和免疫组化法检测NTS前体（ProNTS）、NTS和NTSR 1在胶质瘤中的表达。通过R2微阵列平台从互联网上进行预后分析。CCK 8和BrdU掺入法检测胶质瘤细胞增殖。采用创伤愈合模型和Matrigel transwell法检测细胞迁移和侵袭能力。建立原位胶质瘤移植模型，分析NTS和NTSR 1在体内胶质瘤进展中的作用。NTS和NTSR 1的表达水平与胶质瘤的病理分级呈正相关。NTS和NTSR 1的高表达水平提示胶质瘤患者预后较差。NTS刺激可增强胶质瘤细胞的增殖和侵袭能力，而抑制NTSR 1则可减弱胶质瘤细胞的增殖和侵袭能力。NTS刺激神经胶质瘤细胞中Erk 1/2磷酸化，这可以被SR 48692或NTSR 1-siRNA逆转。体内实验表明，SR 48692可显著延长荷胶质瘤小鼠的存活时间，并抑制胶质瘤细胞的侵袭力。NTS通过激活NTSR 1促进胶质瘤的增殖和侵袭。NTS和NTSR 1高表达水平预示胶质瘤患者预后不良。本文的在线版本（doi：10.1186/s12943-015-0290-8）包含补充材料，可供授权用户使用。
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 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. 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. 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. The online version of this article (doi:10.1186/s12943-015-0290-8) contains supplementary material, which is available to authorized users.
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