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XCT/CD44 MODULATION INDUCES THE SENSITIZATION OF NEUROBLASTOMASTEM CELLS TO ETOPOSIDE
Vol 32, Issue 4S1, 2018
Abstract
The current anticancer therapies for human neuroblastoma (NB) include the use of etoposide, a drugthat exerts its cytotoxic effect by inducing oxidative stress. Although the therapeutic approach withetoposide is initially efficacious, subsequently, it selects a chemoresistant cell population, which is able toadapt to the oxidative environment induced by the drug, increasing the levels of intracellular glutathione(GSH). The chemoresistance is also due to the presence of cancer stem cells (CSCs), which have a lowproliferative rate and are less susceptible to therapies acting on highly proliferating cells. Moreover,CSCs expressing CD44, a PKC-alpha-modulated staminality marker, are able to influence GSH levelsby stabilizing xCT, a transporter promoting the influx of cystine, essential for GSH synthesis. Basedon this evidence, our aim was to investigate whether targeting CD44/xCT might be a useful strategy toincrease neuroblastoma sensitivity to etoposide.
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Supporting Agencies
Copyright (c) 2018 A. SPECIALE, B. MARENGO, N. TRAVERSO, L. MONTELEONE, C. CANTONI, S. RAVERA, O. GARBARINO, M.A. PRONZATO, C. DOMENICOTTI
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Medical Genetics, University of Torino Medical School, Italy
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy