title: Antitumorigenic effect of interferon-β by inhibition of undifferentiated glioblastoma cells.
abstract: Glioma stem-like cells (GSCs) are undifferentiated cells that are considered to be an origin of glioblastomas. Furthermore, they may contribute to treatment resistance and recurrence in glioblastomas. GSCs differentiate into differentiated glioma cells (non-glioma stem-like cells: non‑GSCs), and interconversion might occur between GSCs and non-GSCs. We investigated whether interferon-beta (IFN-β) could exert any efficacy towards GSCs or such interconversion processes. The neural stem cell marker CD133 and pluripotency marker Nanog in GSCs were analyzed to evaluate their differentiation levels. GSCs were considered to undergo differentiation into non-GSCs upon serum exposure, since the expression of CD133 and Nanog in the GSCs was negatively affected. Furthermore, the cells regained their undifferentiated features upon removal of the serum. However, we verified that IFN-β reduced cell proliferation and tumor sphere formation in GSCs, and induced suppression of the restoration of such undifferentiated features. In addition, we also confirmed that IFN-β suppressed the acquisition process of undifferentiated features in human malignant glioma cell lines. Our data thus suggest that IFN-β could be an effective agent not only through its cell growth inhibitory effect on GSCs but also as a means of targeting the interconversion between GSCs and non-GSCs, indicating the possibility of IFN-β being used to prevent treatment resistance and recurrence in glioblastomas, via the inhibition of undifferentiated features.
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Yamamuro
authors.affiliation: Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Sano
authors.affiliation: Department of Research Promotion, Japan Agency for Medical Research and Development, Nagoya, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Okamoto
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Ochiai
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohta
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Ogino
authors.affiliation: Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Natsume
authors.affiliation: Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Wakabayashi
authors.affiliation: Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Ueda
authors.affiliation: Department of Functional Morphology, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hara
authors.affiliation: Division of Companion Diagnostics, Department of Pathology of Microbiology, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Yoshino
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Katayama
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005910:Glioma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006023:Glycoproteins / Q000096:biosynthesis; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D016899:Interferon-beta / Q000008:administration & dosage / Q000235:genetics*; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000378:metabolism; D058953:Neural Stem Cells / Q000473:pathology; D010455:Peptides; D015398:Signal Transduction
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; C000606023:PROM1 protein, human; D010455:Peptides; D016899:Interferon-beta