Identification of Cancer Stem Cells in Murine Tumors

2009 Fiscal Year Final Research Report

• Project/Area Number: 20790300
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Gifu University
• Principal Investigator: HIRATA Akihiro Gifu University, 生命科学総合研究支援センター, 助教 (30397327)
• Project Period (FY): 2008 – 2009
• Keywords: がん幹細胞 / 大腸がん / 組織幹細胞 / β-カテニン / Wntシグナル伝達経路

Research Abstract

The presence of cancer stem cells in murine colon tumors was investigated, focusing on the common characteristics with tissue stem cells. Firstly, we examined the underling mechanisms on the control of cellular differentiation and proliferation in the normal colon epithelium and found that the induction of higher level of β-catenin induced the colonic stem cells dividing slowly. Next, we examined the expression pattern of β-catenin in murine colon tumors and found the cells expressing a higher level of β-catenin and dividing more slowly than surrounding tumor cells, indicating the presence of cancer stem-like cells in murine colon tumors.

Research Products

• [Journal Article] Chemopreventive effects of fermented brown rice and rice bran (FBRA) on the inflammation-related colorectal carcinogenesis in Apc^<Min/+> mice. (2010)
  • Author(s): Phutthaphadoong S, Yamada Y, Hirata A, Tomita H, Taguchi A, Hara A, Limtrakul PN, Iwasaki T, Kobayashi H, Mori H.
  • Journal Title: Oncology Reports. 23(1) Pages: 23-59
  • Peer Reviewed
• [Journal Article] Detection of initiation activity of 1, 2-dimethylhydrazine in in vivo medium-term liver initiation assay system using 4-week-old rats without hepatocellular proliferative stimuli during the test chemical treatment period. (2010)
  • Author(s): Asaoka Y, Sakai H, Hirata A, Sasaki J, Goryo M, Miyamoto Y, Yanai T, Masegi T, Okada K.
  • Journal Title: Journal of Veterinary Medical Sciences. 72(1) Pages: 43-53
  • Peer Reviewed
• [Journal Article] Chemopreventive effects of fermented brown rice and rice bran against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanon e-induced lung tumorigenesis in female A/J mice. (2009)
  • Author(s): Phutthaphadoong S, Yamada Y, Hirata A, Tomita H, Taguchi A, Hara A, Limtrakul PN, Iwasaki T, Kobayashi H, Mori H.
  • Journal Title: Oncology Reports. 21(2) Pages: 321-327
  • Peer Reviewed
• [Journal Article] Roles of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 expression and β-catenin activation in gastric carcinogenesis in N-methyl-N-nitrosourea-treated K19-C2mE transgenic mice. (2008)
  • Author(s): Takasu S, Tsukamoto T, Cao X, Toyoda T, Hirata A, Ban H, Yamamoto M, Sakai H, Yanai T, Masegi T, Oshima M, Tatematsu M.
  • Journal Title: Cancer Science. 99(12) Pages: 2356-2364
  • Peer Reviewed
• [Journal Article] Carcinogenic risk of heterocyclic amines in combination-assessment with a liver initiation model. (2008)
  • Author(s): Hirata A, Tsukamoto T, Sakai H, Takasu S, Ban H, Imai T, Totsuka Y, Nishigaki R, Wakabayashi K, Yanai T, Masegi T, Tatematsu M.
  • Journal Title: Food and Chemical Toxicology. 46(6) Pages: 2003-2009
  • Peer Reviewed
• [Journal Article] Further upregulation of β-catenin/Tcf transcription is involved in the development of macroscopic tumors in the colon Apc^<Min/+> mice. (2008)
  • Author(s): Oyama T, Yamada Y, Hata K, Tomita H, Hirata A, Sheng H, Hara A, Aoki H, Kunisada T, Yamashita S, Mori H.
  • Journal Title: Carcinogenesis. 29(3) Pages: 666-672
  • Peer Reviewed
• [Presentation] 獣医病理病態学からみた比較腫瘍学への貢献-犬の血管肉腫の研究を例に- (2010)
  • Author(s): 酒井洋樹、村上麻美、平田暁大、児玉篤史、村井厚子、米丸加余子、丸尾幸嗣、森崇、星野有希、木村透、柳井徳磨
  • Organizer: 第149回日本獣医学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-28
• [Presentation] DNA低メチル化(Global DNA hypomethylation)の胃発がん抑制作用-メチル基転移酵素Dnmt1低発現マウスによる検討- (2010)
  • Author(s): 平田暁大、山田泰広、富田弘之、山下聡、牛島俊和、原明
  • Organizer: 第26回日本毒性病理学会
  • Place of Presentation: 金沢
  • Year and Date: 2010-02-03
• [Presentation] Dkk-1 heterozygousity dose not promote colon tumor development in Apc (Min/+) mice with Sfrps heterozygousity (2009)
  • Author(s): 平田暁大、山田泰広、尾山武、原明
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-02
• [Presentation] Role of epigenetic modifications in colon tumorigenesis (2009)
  • Author(s): 山田泰広、波多野裕一郎、平田暁大、原明
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-02
• [Presentation] Global hypomethylation suppresses inflammation-related colon carcinogenesis in mice (2009)
  • Author(s): 波多野裕一郎、山田泰広、平田暁大、畑和也、田口綾子、境浩康、馬場政司、原明
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] Roles of Bone Marrow Derived Cells in Helicobacter pylori Associated Mouse Gastric Carcinogenesis (2009)
  • Author(s): 高須伸二、豊田武士、時亮、平田暁大、山本昌美、田口修、立松正衞、塚本徹哉
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] 4週齢ラットを用いた中期イニシエーション活性検索法の有用性 (2009)
  • Author(s): 浅岡由次、酒井洋樹、平田暁大、佐々木淳、御領政信、宮本庸平、柳井徳磨、柵木利昭、岡田幸助
  • Organizer: 第36回日本トキシコロジー学会学術年会
  • Place of Presentation: 盛岡
  • Year and Date: 2009-07-06
• [Presentation] N-bis (2-hydroxypropyl) nitrosamine誘発鼻腔内腫瘍に対するp53ノックアウトマウスの発がん感受性 (2009)
  • Author(s): 平田暁大、塚本徹哉、高須伸二、山本昌美、立松正衞、相磯成敏、福島昭治
  • Organizer: 第16回日本がん予防学会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-06-16
• [Presentation] 骨髄移植マウスにおけるHelicobacter感染およびMNU誘発胃癌と骨髄由来細胞の関与 (2009)
  • Author(s): 高須伸二、塚本徹哉、豊田武士、時亮、平田暁大、山本昌美、立松正衞
  • Organizer: 第16回日本がん予防学会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-06-16
• [Presentation] Cyclooxygenase-2阻害剤EtodolacによるDSS誘発Minマウス大腸腫瘍の抑制効果 (2009)
  • Author(s): 塚本徹哉、時亮、豊田武士、高須伸二、齋藤典子、齋藤亜弓、山本昌美、平田暁大、立松正衞、田中卓二
  • Organizer: 第16回日本がん予防学会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-06-16
• [Presentation] Wnt pathwayによる大腸上皮細胞の増殖制御: β-catenin inducibleマウスによる検討 (2009)
  • Author(s): 平田暁大、山田泰広、山下聡、牛島俊和、原明
  • Organizer: 第25回日本毒性病理学会
  • Place of Presentation: 浜松
  • Year and Date: 2009-01-27
• [Presentation] 未分化性の維持と発がん (2008)
  • Author(s): 山田泰広、原明、平田暁大、廣瀬善信、ルドルフイェーニッシュ、森秀樹
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢
  • Year and Date: 20081015-20081017
• [Presentation] The role of DNA methylation in carcinogenesis of the digestive tract (2008)
  • Author(s): 山田泰広、平田暁大、富田弘之、山下聡、森秀樹、牛島俊和、原明
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-04
• [Presentation] The epigenetic transcriptional repression of Wnt antagonist genes in the development of colon tumors in Apc^<Min/+> mice (2008)
  • Author(s): 尾山武、山田泰広、平田暁大、安井由美子、金美慧、甲野裕之、原明、杉江茂幸、田中卓二、森秀樹
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-04
• [Presentation] Role of the canonical Wnt signaling in prolifbration and differentiation of the colonic epithelium cell (2008)
  • Author(s): 平田暁大、山田泰広、山下聡、牛島俊和、原明、森秀樹
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-03
• [Presentation] Beta-catenin accumulation and mutation in gastric cancer in H. pylori in fected and MNU treated K19-C2mE transgenic mice (2008)
  • Author(s): 高須伸二、塚本徹哉、曹雪源、豊田武士、時亮、平田暁大、大島正伸、立松正衞
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-03
• [Remarks] 第26回日本毒性病理学会会長賞(優秀賞)受賞演題:「DNA低メチル化(Global DNA hypomethylation)の胃発がん抑制作用-メチル基転移酵素Dnmt1低発現マウスによる検討-」
• [Remarks] 第25回日本毒性病理学会会長賞(最優秀賞)受賞演題:「Wnt pathwayによる大腸上皮細胞の増殖制御: β-catenin inducibleマウスによる検討」