title: Expression of CD133 and CD44 in glioblastoma stem cells correlates with cell proliferation, phenotype stability and intra-tumor heterogeneity.
abstract: Glioblastoma (GBM) is a heterogeneous tumor of the brain with a poor prognosis due to recurrence and drug resistance following therapy. Genome-wide profiling has revealed the existence of distinct GBM molecular subtypes that respond differently to aggressive therapies. Despite this, molecular subtype does not predict recurrence or drug resistance and overall survival is similar across subtypes. One of the key features contributing to tumor recurrence and resistance to therapy is proposed to be an underlying subpopulation of resistant glioma stem cells (GSC). CD133 expression has been used as a marker of GSCs, however recent evidence suggests the relationship between CD133 expression, GSCs and molecular subtype is more complex than initially proposed. The expression of CD133, Olig2 and CD44 was investigated using patient derived glioma stem-like cells (PDGCs) in vitro and in vivo. Different PDGCs exhibited a characteristic equilibrium of distinct CD133+ and CD44+ subpopulations and the influence of environmental factors on the intra-tumor equilibrium of CD133+ and CD44+ cells in PDGCs was also investigated, with hypoxia inducing a CD44+ to CD133+ shift and chemo-radiotherapy inducing a CD133+ to CD44+ shift. These data suggest that surveillance and modulation of intra-tumor heterogeneity using molecular markers at initial surgery and surgery for recurrent GBM may be important for more effective management of GBM.
authors.affiliation: Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Brown
authors.affiliation: Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Gulay
authors.initials: G
authors.lastname: Filiz
authors.affiliation: Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Daniel
authors.affiliation: Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Hollande
authors.affiliation: Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, Victoria, Australia.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dworkin
authors.affiliation: Department of Surgery (RMH), University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Amiridis
authors.affiliation: Department of Medicine (RMH), University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Nicole
authors.initials: N
authors.lastname: Kountouri
authors.affiliation: Department of Medicine (RMH), University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Wayne
authors.initials: W
authors.lastname: Ng
authors.affiliation: Department of Medicine (RMH), University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Morokoff
authors.affiliation: Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Theo
authors.identifier: http://orcid.org/0000-0003-3971-5380
authors.initials: T
authors.lastname: Mantamadiotis
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D000860:Hypoxia; D051379:Mice; D008807:Mice, Inbred BALB C; D009364:Neoplasm Recurrence, Local; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D010641:Phenotype
chemical_list: D000071916:AC133 Antigen; D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D018960:Hyaluronan Receptors; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; C497483:CD44 protein, human; C405708:OLIG2 protein, human