title: Isolation of glioma cancer stem cells in relation to histological grades in glioma specimens.
abstract: OBJECTIVE
  The existence of cancer stem cells (CSCs) in glioblastoma has been proposed. However, the unknown knowledge that is yet to be revealed is the presence of glioma CSCs (gCSCs) in correlation to each WHO grades of glioma. We approached this study with a hypothesis that specimens from high-grade gliomas would have higher isolation rate of gCSCs in comparison to those of lower-grade gliomas.
  
  
  METHODS
  The glioma specimens were obtained from patients and underwent gliomasphere assay. The gliomaspheres were chosen to be analyzed with immunocytochemisty for surface markers. Then the selected gliomaspheres were exposed to neural differentiation conditions. Lastly, we made mouse orthotopic glioma models to examine the capacity of gliomagenesis.
  
  
  RESULTS
  The gliomaspheres were formed in WHO grade IV (13 of 21) and III (two of nine) gliomas. Among them, WHO grade IV (11 of 13) and III (two of two) gliomaspheres showed similar surface markers to gCSCs and were capable of neural differentiation. Lastly, among the chosen cells, 10 of 11 WHO grade IV and two of two WHO grade III gliomaspheres were capable of gliomagenesis. Thus, overall, the rates of existence of gCSCs were more prominent in high-grade gliomas: 47.6% (10 of 21) in WHO grade IV gliomas and 22.2% (two of nine) in WHO grade III gliomas, whereas WHO grade II and I gliomas showed virtually no gCSCs.
  
  
  CONCLUSIONS
  This trend of stage-by-stage increase of gCSCs in gliomas showed statistical significance by chi-square test linear-by-linear association. We prove that the rates of existence of gCSCs increase proportionally as the WHO grades of gliomas rise.
authors.affiliation: Department of Medical Science, The Catholic University of Korea College of Medicine, Seoul, South Korea.
authors.forename: Byung Ho
authors.initials: BH
authors.lastname: Kong
authors.forename: Na-Ri
authors.initials: NR
authors.lastname: Park
authors.forename: Jin-Kyoung
authors.initials: JK
authors.lastname: Shim
authors.forename: Bo-Kyung
authors.initials: BK
authors.lastname: Kim
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Shin
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: Huh
authors.forename: Su-Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Eui-Hyun
authors.initials: EH
authors.lastname: Kim
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Park
authors.forename: Jong Hee
authors.initials: JH
authors.lastname: Chang
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Kim
authors.forename: Sun Ho
authors.initials: SH
authors.lastname: Kim
authors.forename: Yong-Kil
authors.initials: YK
authors.lastname: Hong
authors.forename: Seok-Gu
authors.initials: SG
authors.lastname: Kang
authors.forename: Frederick F
authors.initials: FF
authors.lastname: Lang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D002469:Cell Separation; D002675:Child, Preschool; D005260:Female; D005910:Glioma / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D060787:Neoplasm Grading; D014411:Neoplastic Stem Cells / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays / Q000379:methods