P2X7 receptors and glioma cells
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P2X7 receptors and glioma cells Leticia Scussel Bergamin 1 Received: 17 August 2020 / Accepted: 25 August 2020 # Springer Nature B.V. 2020
Glioma (high-grade gliomas) is the most common and lethal tumor of the central nervous system, and their treatment involves surgical resection, radiotherapy, and chemotherapy, but these therapeutic strategies have shown limited success in increasing patient survival, which is less than 2 years [1]. Therefore, it is extremely important to develop more effective and specific treatments for this cancer type. Several lines of evidence suggest that the presence of microglia/macrophages in the glioma microenvironment is an essential component of proliferation, migration, and cell survival processes [2–4]. In recent years, many studies have been conducted to better understand the mechanisms involved in glioma progression. In this context, the P2X7 receptor (P2X7R) has attracted great interest. In the present work, “P2X7 receptor antagonism inhibits tumors growth in human high-grade gliomas”, the authors put forward a hypothesis largely based on previous studies from their laboratory: (i) glioma tumor cells and tumor-associated microglia from human gliomas express P2X7R, and the latter presents functional P2X7R with pore opening ability [5]; (ii) P2X7R pore activation causes IL-1β release, which in turn drives microglia activation and proliferation [6]. This is in keeping with previous reports showing that the P2X7R promotes glioma growth and progression [7–11], though other studies show that P2X7R inhibition increases in vitro and in vivo glioma growth [12, 13]. A possible explanation for these contrasting results could be the heterogeneity of glioma models used (cell lines isolated from mouse, rat, and human), since each cell line has its own characteristics and different
* Leticia Scussel Bergamin [email protected] 1
Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Via Fossato di Mortara, 74, 44121 Ferrara, Italy
levels of P2X7R expression [14]. Therefore, the role of P2X7R in glioma growth remains unclear. The paper by Kan and collaborators sheds new light on the role played by the P2X7R in high-grade glioma growth. In this study, the effect of P2X7R antagonists (brilliant blue G (BBG), oxidized ATP (oATP), and AZ10606120) on the U251 glioma cell line and in human primary cells from patients with highgrade glioma was investigated. The use of human primary glioma cells is of great experimental value because this cell model might retain in vitro some of the properties dictated by glioma microenvironment, providing crucial information on the regulation of P2X7R responses in the tumor core. Moreover, the authors compared the effect of AZ10606120 with temozolomide (chemotherapy agent used to treat glioma patients, but this molecule only increases the survival by few months). The authors confirmed the presence of the P2X7R in glioma and its sensitivity to AZ10606120, BBG, or oATPmediated inhibition. However, only AZ10606120 decreased prolifera
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