Analysis of metabloic characteristics of glioma stem cells

• Project/Area Number: 26861168
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Keio University
• Principal Investigator: Sampetrean Oltea 慶應義塾大学, 医学部, 特任助教 (50571113)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 幹細胞 / 癌

Outline of Final Research Achievements

The objective of this study was to analyze the metabolic characteristics of glioma stem cells (GSCs) and identify related targetable factors. With the use of a mouse model of glioblastoma, we established GSCs that rely on glycolysis and GSCs that obtain energy mainly through the tricarboxylic acid cycle and investigated their metabolic characteristics. For each GSC fraction, we identified their preferential substrates and the enzymes supporting their metabolic profile. Furthermore, we showed that GSCs that can use the TCA cycle under normal conditions can flexibly switch to glycolysis in hypoxic conditions and that they display metabolic plasticity.

Research Products

• [Journal Article] The EGF receptor promotes the malignant potential of glioma by regulating amino acid transport system xc(-) (2016)
  • Author(s): Tsuchihashi K, Okazaki S, Ohmura M, Ishikawa M, Sampetrean O, Onishi N, Wakimoto H, Yoshikawa M, Seishima R, Iwasaki Y, Morikawa T, Abe S, Takao A, Shimizu M, Masuko T, Nagane M, Furnari FB, Akiyama T, Suematsu M, Baba E, Akashi K, Saya H and Nagano O
  • Journal Title: Cancer Res Volume: in press
  • Peer Reviewed
• [Journal Article] Effects of fractionated radiation on murine glioma stem cell metabolism (2016)
  • Author(s): Fujita S, Osuka S, Shibao S, Igarashi K, Soga T, Sampetrean O
  • Journal Title: Toho J Med Volume: in press
  • NAID: 120006412373
  • Peer Reviewed
• [Journal Article] Dynamic epigenetic regulation of glioblastoma tumorigenicity through LSD1 modulation of MYC expression (2015)
  • Author(s): Kozono D, Li J, Nitta M, Sampetrean O, Gonda D, Kushwaha DS, Merzon D, Ramakrishnan V, Zhu S, Zhu K, Matsui H, Harismendy O, Hua W, Mao Y, Kwon CH, Saya H, Nakano I, Pizzo DP, VandenBerg SR and Chen CC
  • Journal Title: Proc Natl Acad Sci USA Volume: 112 Issue: 30 Pages: 112-130
  • DOI: 10.1073/pnas.1501967112
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Integrated analysis identifies different metabolic signatures for tumor-initiating cells in a murine glioblastoma model (2014)
  • Author(s): Saga I, Shibao S, Okubo J, Osuka S, Kobayashi Y, Yamada S, Fujita S, Urakami K, Kusuhara M, Yoshida K, Saya H, Sampetrean O
  • Journal Title: Neuro Oncol. Volume: 16 Issue: 8 Pages: 1048-1056
  • DOI: 10.1093/neuonc/nou096
  • Peer Reviewed / Open Access
• [Presentation] Metabolic characteristics of stem cells during glioma formation (2016)
  • Author(s): Sampetrean O
  • Organizer: Tenth AACR-JCA Joint Conference on Breakthroughs in Cancer
  • Place of Presentation: Maui (USA)
  • Year and Date: 2016-02-18
  • Int'l Joint Research
• [Presentation] 脳腫瘍幹細胞の代謝特性 (2014)
  • Author(s): サンペトラ オルテア
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-26
  • Invited
• [Presentation] Integrated analysis identifies different metabolic signatures within both tumor-initiating cells and stem cells in a murine glioblastoma model (2014)
  • Author(s): Sampetrean O, Saya H
  • Organizer: 20th International Conference on Brain Tumor Research and Therapy
  • Place of Presentation: Lake Tahoe, CA, USA
  • Year and Date: 2014-07-21
• [Presentation] Crosstalk between initiating cells with different metabolism in a murine model of malignant glioma (2014)
  • Author(s): 2.Sampetrean O, Saga I, Shibao S, Okubo J, Osuka S, Onishi N, Fujita S, Saya H
  • Organizer: 105 Annual Meeting of American Association for Cancer Research
  • Place of Presentation: San Diego, USA
  • Year and Date: 2014-04-07
• [Remarks] 慶應義塾大学医学部 遺伝子制御研究部門 ホームページ
  • URL: http://www.genereg.jp/
• [Remarks] 慶應義塾大学医学部 遺伝子制御研究部門 ホームページ
• [Remarks] http://www.genereg.jp