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室管膜下区,成人和儿童高级别胶质瘤干细胞的藏身之处。

The Subventricular Zone, a Hideout for Adult and Pediatric High-Grade Glioma Stem Cells.

作者信息

Lombard Arnaud, Digregorio Marina, Delcamp Clément, Rogister Bernard, Piette Caroline, Coppieters Natacha

机构信息

Laboratory of Nervous System Disorders and Therapy, Groupement Interdisciplinaire de Génoprotéomique Appliquée (GIGA)-Neurosciences Research Centre, University of Liège, Liège, Belgium.

Department of Neurosurgery, CHU of Liège, Liège, Belgium.

出版信息

Front Oncol. 2021 Jan 26;10:614930. doi: 10.3389/fonc.2020.614930. eCollection 2020.

Abstract

Both in adult and children, high-grade gliomas (WHO grades III and IV) account for a high proportion of death due to cancer. This poor prognosis is a direct consequence of tumor recurrences occurring within few months despite a multimodal therapy consisting of a surgical resection followed by chemotherapy and radiotherapy. There is increasing evidence that glioma stem cells (GSCs) contribute to tumor recurrences. In fact, GSCs can migrate out of the tumor mass and reach the subventricular zone (SVZ), a neurogenic niche persisting after birth. Once nested in the SVZ, GSCs can escape a surgical intervention and resist to treatments. The present review will define GSCs and describe their similarities with neural stem cells, residents of the SVZ. The architectural organization of the SVZ will be described both for humans and rodents. The migratory routes taken by GSCs to reach the SVZ and the signaling pathways involved in their migration will also be described hereafter. In addition, we will debate the advantages of the microenvironment provided by the SVZ for GSCs and how this could contribute to tumor recurrences. Finally, we will discuss the clinical relevance of the SVZ in adult GBM and pediatric HGG and the therapeutic advantages of targeting that neurogenic region in both clinical situations.

摘要

在成人和儿童中,高级别胶质瘤(世界卫生组织III级和IV级)在癌症死亡中占比很高。尽管采取了包括手术切除、化疗和放疗在内的多模式治疗,但这种不良预后是肿瘤在数月内复发的直接后果。越来越多的证据表明,胶质瘤干细胞(GSCs)促成了肿瘤复发。事实上,GSCs可以从肿瘤块中迁移出来,到达室下区(SVZ),这是出生后持续存在的神经源性微环境。一旦在SVZ中定植,GSCs就能逃避手术干预并抵抗治疗。本综述将定义GSCs,并描述它们与SVZ中的神经干细胞(SVZ的常驻细胞)的相似之处。将描述人类和啮齿动物的SVZ的结构组织。下文还将描述GSCs到达SVZ所采用的迁移途径以及参与其迁移的信号通路。此外,我们将讨论SVZ为GSCs提供的微环境的优势以及这如何促成肿瘤复发。最后,我们将讨论SVZ在成人胶质母细胞瘤和儿童高级别胶质瘤中的临床相关性,以及在这两种临床情况下靶向该神经源性区域的治疗优势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15d3/7870981/74f20583dde9/fonc-10-614930-g001.jpg

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