Involvement of cancer stem cells in the failure of curative treatment

• Project/Area Number: 21791366
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Cerebral neurosurgery
• Research Institution: Ehime University
• Principal Investigator: TAKAHASHI Hisaaki Ehime University, 大学院・医学系研究科, 講師 (20363228)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: グリオブラストーマ / 腫瘍幹細胞 / 浸潤 / マトリックスメタロプロテアーゼ / グリオーマ

Research Abstract

Glioblastoma has been shown to contain a small population of cancer stem cells. Recent studies have suggested that cancer stem cells cause tumor recurrence based on their resistance to radiotherapy and chemotherapy. Although the highly invasive nature of glioblastoma cells is also implicated in the failure of current therapies, little is known whether cancer stem cells are involved in invasiveness. In this study, we isolated cancer stem-like from a human glioblastoma cell line, U251, and assessed their migratory and invasive ability. These cells showed the enhanced migratory and invasive ability on both in vitro and in vivo. The highly invasive potential of cancer stem cells depends on MMP-13 enzymatic activity, thus MMP-13 might be a potential therapeutic target for glioblastomas.

Research Products

• [Journal Article] Cancer stem-like cells of glioblastoma characteristically express MMP-13 and display highly invasive activity. (2010)
  • Author(s): A.Inoue, H.Takahashi, H.Harada, S.Kohno, S.Ohue, K.Kobayashi, H.Yano, J.Tanaka, T.Ohnishi.
  • Journal Title: International J.Oncology 37 Pages: 1121-1131
  • Peer Reviewed
• [Journal Article] Iba1(+)/NG2(+) macrophage-like cells expressing a variety of neuroprotective factors ameliorate ischemic damage of the brain. (2010)
  • Author(s): A.Smirkin, H.Matsumoto, H.Takahashi, A.Inoue, M.Tagawa, S.Ohue, H.Watanabe, H.Yano, Y.Kumon, T.Ohnishi, J.Tanaka.
  • Journal Title: J Cereb Blood Flow Metab. 30 Pages: 603-615
  • Peer Reviewed
• [Journal Article] Cancer stem-like cells of glioblastoma characteristically express MMP-13 and display highly invasive activity. (2010)
  • Author(s): A.Inoue, H.Takahashi, H.Harada, S.Kohno, S.Ohue, K.Kobayashi, H.Yano, J.Tanaka, T.Ohnishi.
  • Journal Title: International J.Oncology Volume: 37 Pages: 1121-1131
  • Peer Reviewed
• [Journal Article] APP/PS1 double mutant mouse and in Alzheimer's disease. (2010)
  • Author(s): H.Takahashi, I.Brasnjevic, B.P.Rutten, N.Van Der Kolk, D.P.Perl, C.Bouras, H.W.Steinbusch, C.Schmitz, P.R.Hof, D.L.Dickstein.
  • Journal Title: Brain Struct.Funct. Volume: 214 Pages: 145-160
  • Peer Reviewed
• [Journal Article] Iba1(+)/NG2(+) macrophage-like cells expressing a variety of neuroprotective factors ameliorate ischemic damage of the brain. (2010)
  • Author(s): A.Smirkin, H.Matsumoto, H.Takahashi, A.Inoue, M.Tagawa, S.Ohue, H.Watanabe, H.Yano, Y.Kumon T.Ohnishi, J.Tanaka.
  • Journal Title: J Cereb Blood Flow Metab. Volume: 30 Pages: 603-615
  • Peer Reviewed
• [Journal Article] Hippocampal interneuron loss in an APP/PS1 double mutant mouse and in Alzheimer's disease (2010)
  • Author(s): Takahashi H, et al
  • Journal Title: Brain Structure Function 214 Pages: 145-160
  • Peer Reviewed
• [Journal Article] lba1+/NG2+ macrophage-like cells expressing a variety of neuroprotective factors ameliorate ischemic damaqe of the brain (2010)
  • Author(s): Smirkin A, et al
  • Journal Title: J.Cereb.Blood Flow Metab. 30 Pages: 603-615
  • Peer Reviewed
• [Presentation] 膠芽腫における腫瘍幹細胞の性状解析と浸潤能の検討 (2010)
  • Author(s): 高橋寿明
  • Organizer: Neuro2010 日本神経科学大会
  • Place of Presentation: 神戸
• [Presentation] 膠芽腫における腫瘍幹細胞の浸潤能の検討 (2009)
  • Author(s): Inoue A, et al
  • Organizer: 第27回日本脳腫瘍学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-11-09
• [Presentation] Spheres isolated from human glioblastoma promote tumor progression and possess cancer stem cell-like phenotype (2009)
  • Author(s): Takahashi H, et al
  • Organizer: 9th European meeting of Glial cells
  • Place of Presentation: Paris (France)
  • Year and Date: 2009-09-10
• [Presentation] Disruption of LIM-Kinase 2 modulates hippocampal neurodege neration by requlating ER-calcium release (2009)
  • Author(s): Takahashi H, et al
  • Organizer: 36th Congress of the International Union of Physiological Science
  • Place of Presentation: Kyoto (Japan)
  • Year and Date: 2009-07-29
• [Presentation] Characterization of cancer stem cells in human glioblastomas (2009)
  • Author(s): Inoue A, et al
  • Organizer: 第3回国際脳腫瘍学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-05-12
• [Presentation] Spheres isolated from human glioblastoma promote tumor progression and possess cancer stem cell-like phenotype (2009)
  • Author(s): H.Takahashi
  • Organizer: 9th European meeting of Glial cells
  • Place of Presentation: フランス(パリ)
• [Presentation] Spheres isolated from human glioblastoma promote tumor progression and possess cancer stem cell-like phenotype. (2009)
  • Author(s): H.Takahashi, A.Inoue, H.Harada, T.Ohnishi, J.Tanaka
  • Organizer: 9th European meeting of Glial cells
  • Place of Presentation: フランス(パリ)
• [Remarks] ホームページ
  • URL: http://www.proteo.ehime-u.ac.jp/
• [Remarks]
  • URL: http://www.proteo.ehime-u.ac.jp/
• [Remarks]
  • URL: http://www.proteo.ehime-u.ac.jp/