Ammer Laura-Marie, Vollmann-Zwerenz Arabel, Ruf Viktoria, Wetzel Christian H, Riemenschneider Markus J, Albert Nathalie L, Beckhove Philipp, Hau Peter
Wilhelm Sander-NeuroOncology Unit and Department of Neurology, University Hospital Regensburg, 93053 Regensburg, Germany.
Center for Neuropathology and Prion Research, Ludwig Maximilians University of Munich, 81377 Munich, Germany.
Cancers (Basel). 2020 Oct 14;12(10):2973. doi: 10.3390/cancers12102973.
Glioblastoma (GBM) is the most fatal primary brain cancer in adults. Despite extensive treatment, tumors inevitably recur, leading to an average survival time shorter than 1.5 years. The 18 kDa translocator protein (TSPO) is abundantly expressed throughout the body including the central nervous system. The expression of TSPO increases in states of inflammation and brain injury due to microglia activation. Not least due to its location in the outer mitochondrial membrane, TSPO has been implicated with a broad spectrum of functions. These include the regulation of proliferation, apoptosis, migration, as well as mitochondrial functions such as mitochondrial respiration and oxidative stress regulation. TSPO is frequently overexpressed in GBM. Its expression level has been positively correlated to WHO grade, glioma cell proliferation, and poor prognosis of patients. Several lines of evidence indicate that TSPO plays a functional part in glioma hallmark features such as resistance to apoptosis, invasiveness, and proliferation. This review provides a critical overview of how TSPO could regulate several aspects of tumorigenesis in GBM, particularly in the context of the hallmarks of cancer proposed by Hanahan and Weinberg in 2011.
胶质母细胞瘤(GBM)是成人中最致命的原发性脑癌。尽管进行了广泛的治疗,但肿瘤仍不可避免地复发,导致平均生存时间短于1.5年。18 kDa转位蛋白(TSPO)在包括中枢神经系统在内的全身大量表达。由于小胶质细胞激活,TSPO的表达在炎症和脑损伤状态下会增加。尤其是由于其位于线粒体外膜,TSPO与广泛的功能有关。这些功能包括增殖、凋亡、迁移的调节,以及线粒体呼吸和氧化应激调节等线粒体功能。TSPO在GBM中经常过度表达。其表达水平与世界卫生组织(WHO)分级、胶质瘤细胞增殖以及患者的不良预后呈正相关。多项证据表明,TSPO在胶质瘤的标志性特征(如抗凋亡、侵袭性和增殖)中发挥功能性作用。本综述对TSPO如何调节GBM肿瘤发生的多个方面进行了批判性概述,特别是在2011年Hanahan和Weinberg提出的癌症标志的背景下。