Investigation of cancer stem cell system in hepatocellular carcinoma

• Project/Area Number: 19790468
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Chiba University
• Principal Investigator: CHIBA Tetsuhiro Chiba University, 大学院医学研究院, 助教 (00381583)
• Co-Investigator(Renkei-kenkyūsha): IWAMA Atsushi 千葉大学, 大学院医学研究院, 教授 (70244126) ; MIYAGI Satoru 千葉大学, 大学院医学研究院, 助教 (20400997) ; YOKOSUKA Osamu 千葉大学, 大学院医学研究院, 教授 (90182691)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: 癌幹細胞 / 肝臓癌 / 自己複製能 / Bmi1 / CD133, CD90 / Bmil / CD133 / CD90 / フローサイトメトリー / 自己複製 / SP細胞

Research Abstract

肝癌における癌幹細胞システムの解明を目的とし、肝癌臨床検体からの癌幹細胞分離と、ヒト肝癌培養細胞およびマウス肝幹細胞を用いた癌幹細胞システムの検証を行った。肝癌臨床検体からは、CD133 陽性細胞、CD90 陽性細胞を検出できた。また、肝癌培養細胞から分離したsidepopulation 細胞が癌幹細胞として機能し、その腫瘍形成能がBmi1 によって維持されていることや、Bmi1 を強制発現した肝幹細胞において、Bmi1 の主要な標的分子であるInk4a/Arf 遺伝子以外に、より緊密に癌化機転に寄与する分子群の存在を見出した。

Research Products

• [Journal Article] Distinct expression of polycomb group proteins EZH2 and BMI1 in hepatocellular carcinoma (2009)
  • Author(s): Yonemitsu Y.
  • Journal Title: Human Pathology (in press)
  • Peer Reviewed
• [Journal Article] Stem cells and cancer in the liver. (2008)
  • Author(s): Taniguchi H, Chiba T.
  • Journal Title: Dis Markers 24 Pages: 223-229
  • Peer Reviewed
• [Journal Article] The polycomb gene product BMI1 contributes to the maintenance of tumor-initiating side population cells in hepatocellular carcinoma. (2008)
  • Author(s): Chiba T, Miyagi S, Saraya A, Ryutaro Aoki R, Seki A, Morita Y, Yonemitsu Y, Yokosuka O, Taniguchi H, Nakauchi H,Iwama A.
  • Journal Title: Cancer Res 68 Pages: 7742-7749
  • Peer Reviewed
• [Journal Article] The polycomb gene product BMI1 contributes to the maintenance of tumorinitiating side population cells in hepatocellular carcinoma (2008)
  • Author(s): Chiba T.
  • Journal Title: Cancer Research 68 Pages: 7742-7749
  • Peer Reviewed
• [Journal Article] Enhanced self-renewal capability in hepatic stem/progenitor cells drives cancer initiation. (2007)
  • Author(s): Chiba T, Zheng YW, Kita K, Yokosuka O, Saisho H, Onodera M, Miyoshi M, Nakano M, Nakauchi H, Iwama A, Taniguchi H.
  • Journal Title: Gastroenterology 133 Pages: 937-950
  • Peer Reviewed
• [Journal Article] Enhanced self-renewal capability in hepatic stem/progenitor cells drives cancer initiation. (2007)
  • Author(s): Chiba T, et. al.
  • Journal Title: Gastroenterology 133 Pages: 937-950
  • Peer Reviewed
• [Journal Article] Distinct expression of polycomb group proteins EZH2 and BMI1 in hepatocellular carcinoma.
  • Author(s): Yonemitsu Y, Imazeki F, Chiba T, Fukai K, Nagai Y, Miyagi S, Arai M, Aoki R, Miyazaki M, Nakatani Y, Iwama A, Yokosuka O.
  • Journal Title: Hum Pathol (in press.)
  • Peer Reviewed
• [Presentation] Molecular machinery in the establishment and maintenance of liver cancer stem cell system. (2008)
  • Author(s): 千葉哲博、宮城聡、横須賀收、岩間厚志
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 愛知県
  • Year and Date: 2008-10-29
• [Presentation] Molecular machinery in the establishment and maintenance of liver cancer stem cell system (2008)
  • Author(s): 千葉哲博
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-29
• [Presentation] 肝臓における癌幹細胞システムの成立・維持メカニズム (2008)
  • Author(s): 千葉哲博、横須賀收、岩間厚志
  • Organizer: 第16回日本消化器病学会関連週間
  • Place of Presentation: 東京都
  • Year and Date: 2008-10-01
• [Presentation] 肝臓における癌幹細胞システムの成立・維持メカニズム (2008)
  • Author(s): 千葉哲博
  • Organizer: 第16回日本消化器病学会関連週間
  • Place of Presentation: グランドプリンスホテル高輪
  • Year and Date: 2008-10-01
• [Presentation] The polycomb gene product BMI1 is required for the tumor-initiating capacity of hepatocellular carcinoma cells. (2007)
  • Author(s): 千葉哲博、宮城聡、横須賀收、岩間厚志
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 神奈川県
  • Year and Date: 2007-10-03
• [Presentation] ポリコーム遺伝子産物Bmi1は肝癌細胞の腫瘍形成能維持に必須である (2007)
  • Author(s): 千葉哲博
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-03
• [Presentation] Investigation of cancer stem cell system in hepatocellular carcinoma. (2007)
  • Author(s): Chiba T, Miyagi S, Yokosuka O, Taniguchi H, Nakauchi H, Iwama A.
  • Organizer: 17th APASL conference
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2007-03-29