Abstract
Simple SummaryThe translocator protein (TSPO) has been under extensive investigation as a specific marker in positron emission tomography (PET) to visualize brain lesions following injury or disease. In recent years, TSPO is increasingly appreciated as a potential novel therapeutic target in cancer. In Glioblastoma (GBM), the most malignant primary brain tumor, TSPO expression levels are strongly elevated and scientific evidence accumulates, hinting at a pivotal role of TSPO in tumorigenesis and glioma progression. The aim of this review is to summarize the current literature on TSPO with respect to its role both in diagnostics and especially with regard to the critical hallmarks of cancer postulated by Hanahan and Weinberg. Overall, our review contributes to a better understanding of the functional significance of TSPO in Glioblastoma and draws attention to TSPO as a potential modulator of treatment response and thus an important factor that may influence the clinical outcome of GBM.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.
Highlights
Glioblastoma (GBM) is the most common and most aggressive primary brain cancer with a very low life expectancy after diagnosis [1]
Glioblastoma cells to PK11195 induced time-dependent changes in the regulation of the cell cycle and cell proliferation. These functional effects were most likely achieved by modulating the expression of immediate early genes and cell cycle regulators. These results suggest that translocator protein (TSPO) exerts such effects as a part of the mitochondrial-to-nucleus signaling pathway that modulates nuclear gene expression [127]
We summarized experimental evidence suggesting that TSPO might play a role in most of these hallmarks and may be a central modulator of malignancy in GBM
Summary
Glioblastoma (GBM) is the most common and most aggressive primary brain cancer with a very low life expectancy after diagnosis [1]. It can arise as primary or as secondary tumors through the progression from a lower grade glial tumor [2] and is characterized by highly infiltrative and invasive growth, necrosis, and microvascular proliferation [3,4,5,6]. Mutations in the isocitrate dehydrogenase 1 or 2 gene (IDH1, 2) impair metabolism, leading to a decreased production of bioenergy and intermediates (reviewed in [12,13]) and a better outcome for patients [14,15]
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