title: Changes in the biological characteristics of glioma cancer stem cells after serial in vivo subtransplantation.
abstract: OBJECTIVE
  Currently, the interaction between the niche and glioma cancer stem cells (gCSCs) is gaining attention. However, there are few studies concerned with the effects of repeated exposure to a new microenvironment on gCSCs characteristics. In this study, serial in vivo subtransplantation was performed to create a new microenvironment. We evaluated and compared the biological characteristics of gCSCs after serial in vivo subtransplantation.
  
  
  METHODS
  We cultured gCSCs from human glioma specimens according to cultured gliomasphere methods. The isolated gCSCs were termed zero-generation gCSCs (G0-gCSCs). By subsequent serial subtransplantation, we obtained first-generation gCSCs (G1-gCSCs) and second-generation gCSCs (G2-gCSCs). We evaluated and compared the biological characteristics of G0-gCSCs, G1-gCSCs, and G2-gCSCs. The in vitro characteristics included the morphology, surface marker profiles, and neural differentiation capacity and the in vivo characteristics was the survival of mice xenografts. Additionally, brain sections were analyzed using PCNA, TUNEL, and CD31 staining.
  
  
  RESULTS
  We observed no significant differences in the in vitro characteristics of G0-gCSCs, G1-gCSCs, and G2-gCSCs. However, the survival time of mice glioma xenografts was significantly decreased upon serial subtransplantation. In addition, immunohistochemical analyses showed that the number of TUNEL(+) cells was significantly decreased while the number of CD31(+) cells was significantly increased with serial in vivo subtransplantation.
  
  
  CONCLUSIONS
  There were significant in vivo biological changes in gCSCs upon serial in vivo subtransplantation, which were shorter xenograft survival, increased angiogenesis, and decreased apoptosis. This study suggests that the repeated exposure to new microenvironments may affect the biological changes in gCSCs in vivo.
authors.affiliation: Department of Medical Science, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Ga-Yeong
authors.initials: GY
authors.lastname: Shin
authors.forename: Jin-Kyoung
authors.initials: JK
authors.lastname: Shim
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Shin
authors.forename: Su-Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: Huh
authors.forename: Eui-Hyun
authors.initials: EH
authors.lastname: Kim
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Park
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Jong Hee
authors.initials: JH
authors.lastname: Chang
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Kim
authors.forename: Yong-Kil
authors.initials: YK
authors.lastname: Hong
authors.forename: Sun Ho
authors.initials: SH
authors.lastname: Kim
authors.forename: Seok-Gu
authors.initials: SG
authors.lastname: Kang
authors.forename: Frederick F
authors.initials: FF
authors.lastname: Lang
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001932:Brain Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000502:physiology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005909:Glioblastoma / Q000473:pathology*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation / Q000379:methods; D014411:Neoplastic Stem Cells / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D010455:Peptides / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000379:methods; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D000098853:Podoplanin
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D010455:Peptides; D018809:Proliferating Cell Nuclear Antigen; C490441:Pdpn protein, mouse; D000098853:Podoplanin; C577484:NES protein, human; C577485:Nes protein, mouse