title: CD133 Expression Is Not Synonymous to Immunoreactivity for AC133 and Fluctuates throughout the Cell Cycle in Glioma Stem-Like Cells.
abstract: A transmembrane protein CD133 has been implicated as a marker of stem-like glioma cells and predictor for therapeutic response in malignant brain tumours. CD133 expression is commonly evaluated by using antibodies specific for the AC133 epitope located in one of the extracellular domains of membrane-bound CD133. There is conflicting evidence regarding the significance of the AC133 epitope as a marker for identifying stem-like glioma cells and predicting the degree of malignancy in glioma cells. The reasons for discrepant results between different studies addressing the role of CD133/AC133 in gliomas are unclear. A possible source for controversies about CD133/AC133 is the widespread assumption that expression patterns of the AC133 epitope reflect linearly those of the CD133 protein. Consequently, the readouts from AC133 assessments are often interpreted in terms of the CD133 protein. The purpose of this study is to determine whether and to what extent do the readouts obtained with anti-AC133 antibody correspond to the level of CD133 protein expressed in stem-like glioma cells. Our study reveals for the first time that CD133 expressed on the surface of glioma cells is poorly immunoreactive for AC133. Furthermore, we provide evidence that the level of CD133 occupancy on the surface of glioma cells fluctuates during the cell cycle. Our results offer a new explanation for numerous inconsistencies regarding the biological and clinical significance of CD133/AC133 in human gliomas and call for caution in interpreting the lack or presence of AC133 epitope in glioma cells.
authors.affiliation: Molecular Biology of Neuronal Signals, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany; Institute of Neuropathology, University Medical Centre, Göttingen, Germany.
authors.forename: Alonso
authors.initials: A
authors.lastname: Barrantes-Freer
authors.affiliation: Translational Neurooncology Research Group, Department of Neurosurgery, Johannes Gutenberg University Medical Centre, Mainz, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Renovanz
authors.affiliation: Institute of Toxicology, Johannes Gutenberg University Medical Centre, Mainz, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Eich
authors.affiliation: Translational Neurooncology Research Group, Department of Neurosurgery, Johannes Gutenberg University Medical Centre, Mainz, Germany.
authors.forename: Alina
authors.initials: A
authors.lastname: Braukmann
authors.affiliation: Translational Neurooncology Research Group, Department of Neurosurgery, Johannes Gutenberg University Medical Centre, Mainz, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Sprang
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Pavel
authors.initials: P
authors.lastname: Spirin
authors.affiliation: Molecular Biology of Neuronal Signals, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Pardo
authors.affiliation: Translational Neurooncology Research Group, Department of Neurosurgery, Johannes Gutenberg University Medical Centre, Mainz, Germany.
authors.forename: Alf
authors.initials: A
authors.lastname: Giese
authors.affiliation: Translational Neurooncology Research Group, Department of Neurosurgery, Johannes Gutenberg University Medical Centre, Mainz, Germany; Translational Neurooncology Research Group, Department of Neurosurgery, University Medical Centre, Göttingen, Germany.
authors.forename: Ella L
authors.initials: EL
authors.lastname: Kim
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism*; D018938:Caco-2 Cells; D002455:Cell Division; D045744:Cell Line, Tumor; D000939:Epitopes / Q000276:immunology*; D016195:G2 Phase; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism / Q000503:physiopathology*; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism*; D016196:S Phase
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000939:Epitopes; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides