Establishment of human induced cancer stem cells(iCSCs) and malignant brain tumor models derived from neural stem cells

• Project/Area Number: 22700865
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Carcinogenesis
• Research Institution: Keio University
• Principal Investigator: ONISHI Nobuyuki 慶應義塾大学, 医学部, 特任助教 (40534540)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: NSCs / Brain tumor / mouse tumor model / ALK / グリオブラストーマ(GBM) / 神経幹細胞(NSC) / 活性型ALK / 発がんマウスモデル / 活性型H-RAS / 活性型EGFR

Research Abstract

Neural Stem Cells(NSCs) having self-renewal ability and multipotency are considered as one of the cells-of-origin of Brain tumors. The NSCs transduced with constitutively activated ALK rapidly formed highly proliferative and invasive brain tumors. Histological features of these tumors are similar to those of human glioblastoma maltiforme(GBM) such as necrosis, perivascular cuffing and giant cell formation. Immunohistochemistry analysis revealed that these tumors are positive for glioma markers and proliferation marker. These models are useful for investigating molecular mechanisms of gliomagenesis.

Research Products

• [Journal Article] Modulation of glucose metabolism by CD44 contributes to antioxidant status and drug resistance in cancer cells (2012)
  • Author(s): Tamada M, Nagano O, Tateyama S, Ohmura M, Yae T, Ishimoto T, Sugihara E, Onishi N, Yamamoto T, Yanagawa H, Suematsu M, Saya H
  • Journal Title: Cancer Res Volume: 72 Pages: 1438-48
  • Peer Reviewed
• [Journal Article] Modulation of glucose metabolism by CD44 contributes to antioxidant status and drug resistance in cancer cells (2012)
  • Author(s): Mayumi Tamada, et al
  • Journal Title: Cancer Research Volume: 72 Issue: 6 Pages: 1438-1448
  • DOI: 10.1158/0008-5472.can-11-3024
  • Peer Reviewed
• [Journal Article] Fibroblast Growth Factor-2 Is an Important Factor that Maintains Cellular Immaturity and Contributes to Aggressiveness of Osteosarcoma (2012)
  • Author(s): Shimizu T., et al
  • Journal Title: Mol Cancer Res Volume: 10(3) Issue: 3 Pages: 454-468
  • DOI: 10.1158/1541-7786.mcr-11-0347
  • Peer Reviewed
• [Journal Article] Ink4a and Arf are crucial factors in the determination of the cell of origin and the therapeutic sensitivity of Myc-induced mouse lymphoid tumor (2012)
  • Author(s): Sugihara E, Saya H, et al
  • Journal Title: Oncogene Volume: (印刷中) Issue: 23 Pages: 2849-2861
  • DOI: 10.1038/onc.2011.462
  • Peer Reviewed
• [Journal Article] Establishment of a choriocarcinoma model from immortalized normal extravillous trophoblast cells transduced with HRASV12 (2011)
  • Author(s): Kobayashi Y, Shimizu T, Naoe H, Ueki A, Ishizawa J, Chiyoda T, Onishi N, Sugihara E, Nagano O, Banno K, Kuninaka S, Aoki D, Saya H
  • Journal Title: Am J Pathol Volume: 179 Pages: 1471-82
  • Peer Reviewed
• [Journal Article] Transient depletion of p53 followed by transduction of c-Myc and K-Ras converts ovarian stem-like cells into tumor-initiating cells (2011)
  • Author(s): Motohara T, Masuko S, Ishimoto T, Yae T, Onishi N, Muraguchi T, Hirao A, Matsuzaki Y, Tashiro H, Katabuchi H, Saya H, Nagano O
  • Journal Title: Carcinogenesis Volume: 32 Pages: 1597-606
  • Peer Reviewed
• [Journal Article] Invasion precedes tumor mass formation in a malignant brain tumor model of genetically modified neural stem cells (2011)
  • Author(s): Sampetrean O, Saga I, Nakanishi M, Sugihara E, Fukaya R, Onishi N, Osuka S, Akahata M, Kai K, Sugimoto H, Hirao A, Saya H
  • Journal Title: Neoplasia Volume: 13 Pages: 784-91
  • Peer Reviewed
• [Journal Article] Ink4a and Arf are crucial factors in the determination of the cell of origin and the therapeutic sensitivity of Myc-induced mouse lymphoid tumor (2011)
  • Author(s): Sugihara E, Shimizu T, Kojima K, Onishi N, Kai K, Ishizawa J, Nagata K, Hashimoto N, Honda H, Kanno M, Miwa M, Okada S, Andreeff M and Saya H
  • Journal Title: Oncogene Volume: 31 Pages: 2849-61
  • Peer Reviewed
• [Presentation] 骨肉腫病態形成におけるFgf2の役割 (2011)
  • Author(s): 清水孝恒
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-04
• [Presentation] 誘導脳腫瘍幹細胞を用いた放射線抵抗性獲得モデルの確立 (2011)
  • Author(s): 大須賀覚
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-04
• [Presentation] 神経幹細胞を用いたマウス脳腫瘍モデルの構築 (2011)
  • Author(s): 大西伸幸
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-04
• [Presentation] 骨肉腫病態形成におけるFgf2の役割 (2011)
  • Author(s): 清水孝恒
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知)
  • Year and Date: 2011-10-04
• [Presentation] 誘導脳腫瘍幹細胞を用いた放射線抵抗性獲得モデルの確立 (2011)
  • Author(s): 大須賀覚
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知)
  • Year and Date: 2011-10-04
• [Presentation] 誘神経幹細胞を用いたマウス脳腫瘍モデルの構築 (2011)
  • Author(s): 大西伸幸
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知)
  • Year and Date: 2011-10-04
• [Presentation] グリオーマ幹細胞モデルを用いた薬剤抵抗性克服 (2011)
  • Author(s): Oltea Sampetrean
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-03
• [Presentation] Igf2bp3/Imp3の異常発現は骨肉腫悪性度を決定する (2011)
  • Author(s): 植木有紗
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-03
• [Presentation] Igf2bp3/Imp3の異常発現は骨肉腫悪性度を決定する (2011)
  • Author(s): 植木有紗
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知)
  • Year and Date: 2011-10-03
• [Presentation] グリオーマ幹細胞モデルを用いた薬剤抵抗性克服 (2011)
  • Author(s): Oltea Sampetrean
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知)
  • Year and Date: 2011-10-03
• [Remarks]
  • URL: http://genereg.jp/index.html