title: Glioblastoma stem cells (GSCs) epigenetic plasticity and interconversion between differentiated non-GSCs and GSCs.
abstract: Cancer stem cells (CSCs) or cancer initiating cells (CICs) maintain self-renewal and multilineage differentiation properties of various tumors, as well as the cellular heterogeneity consisting of several subpopulations within tumors. CSCs display the malignant phenotype, self-renewal ability, altered genomic stability, specific epigenetic signature, and most of the time can be phenotyped by cell surface markers (e.g., CD133, CD24, and CD44). Numerous studies support the concept that non-stem cancer cells (non-CSCs) are sensitive to cancer therapy while CSCs are relatively resistant to treatment. In glioblastoma stem cells (GSCs), there is clonal heterogeneity at the genetic level with distinct tumorigenic potential, and defined GSC marker expression resulting from clonal evolution which is likely to influence disease progression and response to treatment. Another level of complexity in glioblastoma multiforme (GBM) tumors is the dynamic equilibrium between GSCs and differentiated non-GSCs, and the potential for non-GSCs to revert (dedifferentiate) to GSCs due to epigenetic alteration which confers phenotypic plasticity to the tumor cell population. Moreover, exposure of the differentiated GBM cells to therapeutic doses of temozolomide (TMZ) or ionizing radiation (IR) increases the GSC pool bothin vitroandin vivo. This review describes various subtypes of GBM, discusses the evolution of CSC models and epigenetic plasticity, as well as interconversion between GSCs and differentiated non-GSCs, and offers strategies to potentially eliminate GSCs.
authors.affiliation: Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA ; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Safa
authors.affiliation: Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA ; Department of Neurosurgery, IU School of Medicine and Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Saadatzadeh
authors.affiliation: Department of Neurosurgery, IU School of Medicine and Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Aaron A
authors.initials: AA
authors.lastname: Cohen-Gadol
authors.affiliation: Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA ; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA ; Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Pollok
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA ; Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Khadijeh
authors.initials: K
authors.lastname: Bijangi-Vishehsaraei
keywords: Cancer stem cells; Dedifferentiation; Epigenetic; GBM plasticity; GBM stem cells; Glioblastoma; Stemness