title: Multidrug resistance in glioblastoma stem-like cells: Role of the hypoxic microenvironment and adenosine signaling.
abstract: Glioblastoma multiforme (GBM) is considered the most common and aggressive tumour of the central nervous system and is characterized for being highly chemoresistant. This property is mainly due to the activation of Multiple Drug Resistance (MDR) mechanisms that protect cancer cells from structurally and morphologically different drugs. Overexpression and increased ABC transporters activity is one of the most important MDR mechanisms at the clinical level, and both its expression and activity are elevated in GBM cells. Within the tumour, there is a subpopulation called glioblastoma stem-like cells (GSCs), which due to its high tumourigenic capacity and chemoresistance, have been postulated as the main responsible for tumour recurrence. The GSCs inhabit hypoxic tumour zones, niches that apart from maintaining and promoting stem phenotype have also been correlated with high chemoresistance. Of the signalling pathways activated during hypoxia, purinergic signalling has been highly associated to the induction of MDR mechanisms. Through its receptors, the nucleoside adenosine has been shown to promotes the chemoresistance mediated by ABC transporters. Therefore, targeting its components is a promising alternative for GBM treatment. In this review, we will discuss chemoresistance in GSCs and the effect of the hypoxic microenvironment and adenosine on MDR mechanisms.
authors.affiliation: Molecular Pathology Laboratory, Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Daniel
authors.initials: D
authors.lastname: Uribe
authors.affiliation: Molecular Pathology Laboratory, Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Ángelo
authors.initials: Á
authors.lastname: Torres
authors.affiliation: Molecular Pathology Laboratory, Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: José Dellis
authors.initials: JD
authors.lastname: Rocha
authors.affiliation: Molecular Pathology Laboratory, Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Niechi
authors.affiliation: Molecular Pathology Laboratory, Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: Oyarzún
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile; Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, Seville E-41012, Spain; University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston QLD 4029, Queensland, Australia.
authors.forename: Luis
authors.initials: L
authors.lastname: Sobrevia
authors.affiliation: Molecular Pathology Laboratory, Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Rody
authors.initials: R
authors.lastname: San Martín
authors.affiliation: Molecular Pathology Laboratory, Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile. Electronic address: claudiaquezada@uach.cl.
authors.forename: Claudia
authors.initials: C
authors.lastname: Quezada
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000241:Adenosine / Q000235:genetics* / Q000378:metabolism; D015687:Cell Hypoxia / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects; D015398:Signal Transduction; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D000241:Adenosine
keywords: ATP-Binding Cassette (ABC) transporter; Adenosine; Glioblastoma multiforme; Glioblastoma stem-like cells; Hypoxia; Multiple Drug Resistance