title: Transforming growth factor-β and stem cell markers are highly expressed around necrotic areas in glioblastoma.
abstract: Invasion into surrounding normal brain and resistance to genotoxic therapies are the main devastating aspects of glioblastoma (GBM). These biological features may be associated with the stem cell phenotype, which can be induced through a dedifferentiation process known as epithelial-mesenchymal transition (EMT). We show here that tumor cells around pseudopalisading necrotic areas in human GBM tissues highly express the most important EMT inducer, transforming growth factor (TGF-β), concurrently with the EMT-related transcriptional factor, TWIST. In addition, the stem cell markers CD133 and alkaline phosphatase (ALPL) were also highly expressed around necrotic foci in GBM tissues. The high expression of TGF-β around necrotic regions was significantly correlated with shorter progression-free survival and overall survival in patients with GBM. High expression of stem cell markers, ALPL, CD133, and CD44 was also correlated with poor outcomes. These results collectively support the hypothesis that tissue hypoxia induces the stem cell phenotype through TGF-β-related EMT and contributes to the poor outcome of GBM patients.
authors.affiliation: Department of Neurological Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-2870, Japan. iwadatey@faculty.chiba-u.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Iwadate
authors.affiliation: Department of Neurological Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-2870, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Matsutani
authors.affiliation: Department of Neurological Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-2870, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Hirono
authors.affiliation: Department of Neurological Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-2870, Japan.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Shinozaki
authors.affiliation: Department of Neurological Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-2870, Japan.
authors.forename: Naokatsu
authors.initials: N
authors.lastname: Saeki
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism; D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D012189:Retrospective Studies; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D009687:Nuclear Proteins; C000606023:PROM1 protein, human; C103173:TWIST1 protein, human; D016212:Transforming Growth Factor beta; D051879:Twist-Related Protein 1; D000469:Alkaline Phosphatase
keywords: EMT; Epithelial-mesenchymal transition; Glioma; Hypoxia; Microenvironment; TGF-β