The Role of Translocator Protein TSPO in Hallmarks of Glioblastoma

Abstract

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.

Inhibition of translocator protein 18 kDa suppressed the progression of glioma via the ELAV-like RNA-binding protein 1/MAPK-activated protein kinase 3 axis

“…Previous clinical research revealed that TSPO expression levels are elevated in various cancers including glioma [ 24 , 25 ], and increased TSPO expression was positively correlated with poor prognosis, as observed in our present study. In fact, the biological function of TSPO in glioma cells had been widely studied.…”

MR susceptibility imaging for detection of tumor-associated macrophages in glioblastoma

“…A variety of MRI and PET imaging techniques have been used to quantify TAMs in gliomas (43), for example, in a pilot study of 10 adult subjects with GBM who underwent ferumoxytol-enhanced MRI, measurements of susceptibility obtained after ferumoxytol administration correlate with iron-containing macrophage concentration (34); however, this approach requires slow intravenous administration of ferumoxytol followed by next day delayed imaging which may limit the widespread use. Translocator protein (TSPO) speci c PET radiotracers have also been used to monitors TAMs; however, the two main limitations are lack of phenotype (M1 vs. M2) speci city (43), and over-expression in tumor cells (44). To the best of our knowledge, our study is the rst to provide both in vivo and ex vivo evidence for the application of non-invasive MRI imaging for TAMs quanti cation and spatial mapping in human GBM.…”

In Vivo Quantitative Imaging of Glioma Heterogeneity Employing Positron Emission Tomography

“…Overall, the authors supported [ 18 F]DPA-714 PET imaging as an imaging readout for the degree of immunosuppressive myeloid cell infiltration. On the other hand, Pannell et al investigated whether TSPO upregulation in astrocytes and microglia/macrophages was restricted to a specific phenotype [44]. TSPO overexpression was observed both in vitro and in vivo after injection of TNF-inducing adenovirus while no change was observed after IL-4 stimulation, correlating with [ 18 F]DPA-714 PET signal.…”

“…Overall, considering the role of TSPO in the regulation of GBM development, the interpretation of the TSPO PET signal is still challenged by the time-dependent cellular sources and functions of TSPO [44]. One recent study by Fu et al (2020) indicated that TSPO appears as a key regulator of glioma growth and especially angiogenesis through the regulation of mitochondrial oxidative phosphorylation and glycolysis [30].…”