title: MET Expressed in Glioma Stem Cells Is a Potent Therapeutic Target for Glioblastoma Multiforme.
abstract: BACKGROUND
  Glioblastoma multiforme (GBM) is the most frequent and the most malignant tumor among adult brain tumors. Previous reports led us to hypothesize that the proto-oncogene mesenchymal-epithelial transition (MET) expressed in glioma stem cell-like cells (GSCs) would be a potent therapeutic target for GBM.
  
  
  METHODS
  To address this question, we analyzed 113 original samples of tumors from patients based on immunohistochemistry. During this process, we were able to establish GSC lines from patients with GBM that were MET-positive and MET-negative. Using these cells, we tested the therapeutic impact of a MET inhibitor, crizotinib, both in vitro and in vivo.
  
  
  RESULTS
  Patients with MET-positive GBM exhibited poor survival. GSC-based experiments revealed that treatment with crizotinib, both in vitro and in vivo, exhibited therapeutic efficacy particularly against MET-positive GSCs.
  
  
  CONCLUSIONS
  Based on these findings, we conclude that MET expressed in GSCs might be a potent therapeutic target for GBM.
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, Kindai University, Osaka, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Tasaki
authors.affiliation: Department of Microbiology, Faculty of Medicine, Kindai University, Osaka, Japan mfujita47@med.kindai.ac.jp.
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Fujita
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, Kindai University, Osaka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okuda
authors.affiliation: Department of Pathology, Faculty of Medicine, Kindai University, Osaka, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Yoneshige
authors.affiliation: Department of Clinical Oncology, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakata
authors.affiliation: Department of Surgery, Division of Gastrointestinal Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, Kindai University, Osaka, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yoshioka
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, Kindai University, Osaka, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Izumoto
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, Kindai University, Osaka, Japan.
authors.forename: Amami
authors.initials: A
authors.lastname: Kato
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D001932:Brain Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D000077547:Crizotinib; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D014411:Neoplastic Stem Cells / Q000201:enzymology*; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: MET; crizotinib; glioblastoma; gloma stem cell