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原癌蛋白 Prosaposin 是间质型神经胶质瘤的生物标志物,通过 TGF-β1/Smad 信号通路调节间质转化。

Prosaposin is a biomarker of mesenchymal glioblastoma and regulates mesenchymal transition through the TGF-β1/Smad signaling pathway.

机构信息

Department of Neurosurgery, The First Hospital of China Medical University, Shenyang City, PR China.

Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.

出版信息

J Pathol. 2019 Sep;249(1):26-38. doi: 10.1002/path.5278. Epub 2019 May 21.

Abstract

Mesenchymal glioblastoma (GBM) is the most aggressive subtype of GBM. Our previous study found that neurotrophic factor prosaposin (PSAP) is highly expressed and secreted in glioma and can promote the growth of glioma. The role of PSAP in mesenchymal GBM is still unclear. In this study, bioinformatic analysis, western blotting and RT-qPCR were used to detect the expression of PSAP in different GBM subtypes. Human glioma cell lines and patient-derived glioma stem cells were studied in vitro and in vivo, revealing that mesenchymal GBM expressed and secreted the highest level of PSAP among four subtypes of GBM, and PSAP could promote GBM invasion and epithelial-mesenchymal transition (EMT)-like processes in vivo and in vitro. Bioinformatic analysis and western blotting showed that PSAP mainly played a regulatory role in GBM invasion and EMT-like processes via the TGF-β1/Smad signaling pathway. In conclusion, the overexpression and secretion of PSAP may be an important factor causing the high invasiveness of mesenchymal GBM. PSAP is therefore a potential target for the treatment of mesenchymal GBM. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

摘要

间质型胶质母细胞瘤(GBM)是 GBM 中侵袭性最强的亚型。我们之前的研究发现,神经营养因子前蛋白聚糖(PSAP)在胶质瘤中高度表达和分泌,并能促进胶质瘤的生长。PSAP 在间质型 GBM 中的作用尚不清楚。在这项研究中,我们通过生物信息学分析、western blot 和 RT-qPCR 检测了不同 GBM 亚型中 PSAP 的表达。在体外和体内研究了人胶质瘤细胞系和患者来源的胶质瘤干细胞,结果表明,在 GBM 的四个亚型中,间质型 GBM 表达和分泌 PSAP 的水平最高,PSAP 可以促进 GBM 的侵袭和体内及体外的上皮间质转化(EMT)样过程。生物信息学分析和 western blot 表明,PSAP 主要通过 TGF-β1/Smad 信号通路在 GBM 的侵袭和 EMT 样过程中发挥调控作用。总之,PSAP 的过表达和分泌可能是导致间质型 GBM 高侵袭性的一个重要因素。因此,PSAP 是治疗间质型 GBM 的一个潜在靶点。

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