論文

査読有り
2019年2月

Induced expression of GINS complex is an essential step for reactivation of quiescent stem-like tumor cells within the peri-necrotic niche in human glioblastoma

Journal of Cancer Research and Clinical Oncology
  • Tokuhiro Kimura
  • ,
  • Dan Cui
  • ,
  • Hiroo Kawano
  • ,
  • Chihiro Yoshitomi-Sakamoto
  • ,
  • Nobuyuki Takakura
  • ,
  • Eiji Ikeda

145
2
開始ページ
363
終了ページ
371
記述言語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s00432-018-2797-z
出版者・発行元
Springer Science and Business Media LLC

© 2018, The Author(s). Purpose: Glioblastoma is still intractable despite the progress in therapies, and the intractability is attributable to a minor population of stem-like tumor cells. As a niche harboring quiescent stem-like tumor cells with potentially high tumorigenicity, we have specified an area around large ischemic necrosis, termed ‘peri-necrotic niche’, in glioblastoma. In this study, the behavior of tumor cells inside and outside the peri-necrotic niche was analyzed to find out molecules responsible for reactivation of quiescent stem-like tumor cells to proliferate outside the niche. Methods: Expression of Ki-67 and GINS complex composed of SLD5, PSF1, PSF2 and PSF3 was analyzed by immunohistochemistry in human glioblastoma tissue samples. Proliferation assays, immunoblotting and siRNA experiments were performed using a glioblastoma cell line. Results: Immunohistochemical analysis revealed quiescent and proliferative phenotypes of tumor cells inside and outside the niche, respectively, and the proliferation was spatially correlated with the expression of GINS components in tumor cells. To mimic the tissue microenvironment inside versus outside the niche, glioblastoma cells were cultured under hypoxic versus normoxic conditions, or without versus with serum. Quiescence and proliferation of tumor cells were reversibly determined by the microenvironment inside and outside the niche, respectively, and proliferative activities paralleled the expression levels of GINS components. Furthermore, the reactivation of proliferation after reoxygenation or serum replenishment was suppressed in quiescent tumor cells with PSF1 knockdown. Conclusions: These findings indicate the essential role of GINS complex in the switch between quiescence and proliferation of tumor cells inside and outside the peri-necrotic niche.

リンク情報
DOI
https://doi.org/10.1007/s00432-018-2797-z
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30465075
URL
http://link.springer.com/article/10.1007/s00432-018-2797-z/fulltext.html
URL
http://link.springer.com/content/pdf/10.1007/s00432-018-2797-z.pdf
Scopus
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85056890799&origin=inward 本文へのリンクあり
Scopus Citedby
https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85056890799&origin=inward
ID情報
  • DOI : 10.1007/s00432-018-2797-z
  • ISSN : 0171-5216
  • eISSN : 1432-1335
  • PubMed ID : 30465075
  • SCOPUS ID : 85056890799

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