Li Chunliu, Zhang Zhen, Lv Peng, Zhan Yan, Zhong Qianwei
Department of Clinical Laboratory, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, People's Republic of China.
Department of Neurology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, People's Republic of China.
Onco Targets Ther. 2020 May 1;13:3677-3687. doi: 10.2147/OTT.S242462. eCollection 2020.
The secretory carrier-associated membrane protein 3 (SCAMP3) is a component of post-Golgi membranes, functions as a protein carrier and is critical for subcellular protein transportation. Limited studies revealed an elevated expression of SCAMP3 in breast cancer and hepatocellular carcinoma; however, its role in glioma remains unknown. The aim of our study is to investigate the expression pattern and functional mechanisms of SCAMP3 in glioma.
mRNA and protein levels of SCAMP3 were examined in glioma tissues together with nontumorous brain tissues by using quantitative real-time-PCR and immunohistochemistry staining. The prognostic role of SCAMP3 in glioma was evaluated through univariate and multivariate analyses. In vitro and in vivo assays were conducted to explore the underlying mechanisms of SCAMP3-induced glioma progression.
The expression level of SCAMP3 was higher in glioma tissues than that in normal brain tissues. High protein level of SCAMP3 was correlated with larger tumor size and advanced WHO grade. Glioma patients with high-SCAMP3 level had worse overall survival. In addition, SCAMP3 was defined as an independent risk factor of glioma prognosis. Cellular and xenograft studies revealed that SCAMP3 promotes glioma proliferation possibly through enhancing EGFR and mTORC1 signaling.
Our studies revealed that high-SCAMP3 expression level was closely related to the unfavorable clinical features and poor prognosis of glioma patients. SCAMP3 may serve as an invaluable prognostic indicator and novel therapeutic target for glioma treatment.
分泌载体相关膜蛋白3(SCAMP3)是高尔基体后膜的一个组成部分,作为一种蛋白质载体发挥作用,对亚细胞蛋白质运输至关重要。有限的研究显示,SCAMP3在乳腺癌和肝细胞癌中表达升高;然而,其在胶质瘤中的作用仍不清楚。我们研究的目的是探讨SCAMP3在胶质瘤中的表达模式和功能机制。
采用定量实时聚合酶链反应和免疫组织化学染色法检测胶质瘤组织及非肿瘤脑组织中SCAMP3的mRNA和蛋白水平。通过单因素和多因素分析评估SCAMP3在胶质瘤中的预后作用。进行体外和体内实验以探究SCAMP3诱导胶质瘤进展的潜在机制。
SCAMP3在胶质瘤组织中的表达水平高于正常脑组织。SCAMP3蛋白水平高与肿瘤体积大及世界卫生组织(WHO)分级高相关。SCAMP3水平高的胶质瘤患者总生存期较差。此外,SCAMP3被确定为胶质瘤预后的独立危险因素。细胞和异种移植研究表明,SCAMP3可能通过增强表皮生长因子受体(EGFR)和哺乳动物雷帕霉素靶蛋白复合体1(mTORC1)信号促进胶质瘤增殖。
我们的研究表明,SCAMP3高表达水平与胶质瘤患者不良的临床特征和预后密切相关。SCAMP3可能作为一种宝贵的预后指标和胶质瘤治疗的新靶点。