Analysis of the maintenance of stemness of glioma initiating cells

• Project/Area Number: 24700966
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: The University of Tokyo
• Principal Investigator: KOMURO AKIYOSHI 東京大学, 医学(系)研究科(研究院), 特任研究員 (50512274)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 癌幹細胞 / 脳腫瘍 / TGF-βファミリーシグナル / BMP / 脳腫瘍幹細胞

Research Abstract

To investigate the effect of TGF-beta family signaling on the stemness of glioma initiating-cells (GICs), we observed that Bone morphogenetic protein 4 (BMP4) had inhibitory effects of the maintenance of stemness of GICs. And we identified novel BMP4 signal target genes in GICs by using gene expression microarray analysis and RNA-seq. Using overexpression or knockdown of these novel BMP4 target genes, we found that these genes were correlated with differentiation and infiltration of GICs. Target therapy of BMP4 signaling target genes may provide a novel strategy for glioma patients.

Research Products

• [Journal Article] TGF-b-induced apoptosis of B-cell lymphoma Ramos cells through reduction of MS4A1/CD20 (2013)
  • Author(s): Kimihiro C. Kawabata, Shogo Ehata, Akiyoshi Komuro, Kengo Takeuchi and Kohei Miyazono
  • Journal Title: Oncogne Volume: 32 (16) Pages: 2096-2106
  • Peer Reviewed
• [Presentation] BMP4 suppresses tumorigenic activity of glioma-initiating cells through loss of stemness properties (2013)
  • Author(s): Akiyoshi Komuro, Satoshi Sakai, Yasushi Ino, Tomoki Todo, Nobuhito Saito, Tetsuro Watabe, Caname Iwata, Daizo Koinuma, Kohei Miyazono
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2013-09-13
• [Presentation] BMP4 suppresses tumorigenic activity of glioma-initiating cells through loss of stemness properties (2013)
  • Author(s): Akiyoshi Komuro, Satoshi Sakai, Erna Raja, Yasushi Ino, Tomoki Todo, Nobuhito Saito, Tetsuro Watabe, Caname Iwata, Daizo Koinuma, Kohei Miyazono
  • Organizer: TGF-βファミリーシグナル国際共同研究拠点第3回国際シンポジウム
  • Place of Presentation: 愛媛
• [Presentation] BMP4 suppresses tumorigenic activity of glioma-initiating cells through loss of stemness properties (2013)
  • Author(s): Akiyoshi Komuro, Hiroaki Ikushima, Satoshi Sakai, Yasushi Ino, Tomoki Todo, Nobuhito Saito, Tetsuro Watabe, Daizo Koinuma, Kohei Miyazono
  • Organizer: Ninth AACR-Japanese Cancer Association Joint Conference
  • Place of Presentation: Maui (USA)
• [Presentation] BMP signaling suppresses tumorigenic activity of glioma-initiating cells through loss of stemness properties (2013)
  • Author(s): Akiyoshi Komuro, Satoshi Sakai, Yasushi Ino, Tomoki Todo, Nobuhito Saito, Tetsuro Watabe, Caname Iwata, Daizo Koinuma, Kohei Miyazono
  • Organizer: FASEB Science Research Conference "TGF-β Superfamily: Signaling in Development & Disease"
  • Place of Presentation: Colorado (USA)
• [Presentation] BMP signaling suppresses tumorigenic activity of glioma-initiating cells through loss of stemness properties (2013)
  • Author(s): Akiyoshi Komuro, Satoshi Sakai, Erna Raja, Yasushi Ino, Tomoki Todo, Nobuhito Saito, Tetsuro Watabe, Caname Iwata, Daizo Koinuma, Kohei Miyazono
  • Organizer: TGF-βファミリーシグナル 国際共同研究拠点 第3回国際シンポジウム
  • Place of Presentation: 愛媛
• [Presentation] BMP4 suppresses tumorigenic activity of glioma-initiating cells through loss of stemness properties (2013)
  • Author(s): Akiyoshi Komuro, Hiroaki Ikushima, Satoshi Sakai, Yasushi Ino, Tomoki Todo, Nobuhito Saito, Tetsuro Watabe, Daizo Koinuma, Kohei Miyazono
  • Organizer: Ninth AACR-Japanese Cancer Association Joint Conference
  • Place of Presentation: Hyatt Regency Maui, Maui, HI, USA
• [Presentation] BMP4 suppresses tumorigenic activity of glioma-initiating cells through loss of stemness properties (2012)
  • Author(s): Akiyoshi Komuro, Hiroaki Ikushima, Satoshi Sakai, Yasushi Ino, Tomoki Todo, Nobuhito Saito, Tetsuro Watabe, Daizo Koinuma, Kohei Miyazono
  • Organizer: 国際癌化学診療シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2012-12-05
• [Presentation] 骨形成因子(BMP)4による膠芽腫腫瘍形成細胞の治療効果の検討 (2012)
  • Author(s): 古室暁義, 生島弘彬, 稲生靖, 藤堂具紀, 渡部徹郎, 鯉沼代造, 宮園浩平
  • Organizer: 第19回BMP研究会
  • Place of Presentation: 東京
  • Year and Date: 2012-07-22
• [Presentation] Glioma Cancer Initiating Cellを標的としたTGF-βシグナル阻害剤とBMP4の併用治療効果の検討 (2012)
  • Author(s): 古室暁義, 生島弘彬, 江幡正悟, 渡部徹郎, 鯉沼代造, 稲生靖, 藤堂具紀, 宮園浩平
  • Organizer: 第16回日本がん分子標的治療学会学術集会
  • Place of Presentation: 福岡
• [Presentation] Glioma Cancer Initiating Cell を標的としたTGF-βシグナル阻害剤とBMP4の併用治療効果の検討 (2012)
  • Author(s): 古室 暁義 , 生島 弘彬, 江幡 正悟, 渡部 徹郎, 鯉沼 代造, 稲生 靖, 藤堂 具紀, 宮園 浩平
  • Organizer: 第16回日本がん分子標的治療学会学術集会
  • Place of Presentation: 西日本総合展示場 AIM3F （福岡県）
• [Presentation] 骨形成因子（BMP）4による膠芽腫腫瘍形成細胞の治療効果の検討 (2012)
  • Author(s): 古室暁義, 生島弘彬, 稲生 靖, 藤堂具紀, 渡部徹郎, 鯉沼代造, 宮園浩平
  • Organizer: 第19回BMP研究会
  • Place of Presentation: 慶応大学医学部信濃町キャンパス （東京都）
• [Presentation] BMP4 suppresses tumorigenic activity of glioma-initiating cells through loss of stemness properties (2012)
  • Author(s): Akiyoshi Komuro, Hiroaki Ikushima, Satoshi Sakai, Yasushi Ino, Tomoki Todo, Nobuhito Saito, Tetsuro Watabe, Daizo Koinuma, Kohei Miyazono
  • Organizer: 国際癌化学診療シンポジウム
  • Place of Presentation: 日本科学未来館 （東京都）
• [Presentation] BMP signaling suppresses tumorigenic activity of glioma-initiating cells through loss of stemness properties
  • Author(s): Akiyoshi Komuro, Satoshi Sakai, Yasushi Ino, Tomoki Todo, Nobuhito Saito, Tetsuro Watabe, Caname Iwata, Daizo Koinuma, Kohei Miyazono
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
• [Book] 治療の分子標的としてのTGF-βシグナル, 日本臨床 (70巻増刊号8, 通巻1031号) (2012)
  • Author(s): 古室暁義, 宮園浩平