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Isolation and characterization of stomach and colon cancer stem cells in human

Research Project

Project/Area Number 20591531
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionYokohama City University

Principal Investigator

ZHENG Yun-Wen  Yokohama City University, 医学部, 助教 (80404995)

Co-Investigator(Kenkyū-buntansha) TANIGUCHI Hideki  横浜市立大学, 医学研究科, 教授 (70292555)
UENO Yasuharu  横浜市立大学, 医学部, 助教 (60375235)
Research Collaborator KOZAWA Mayumi  横浜市立大学, 大学院・医学研究科・消化器病態外科学, 大学院生
MIYATA Hidetoshi  横浜市立大学, 大学院・医学研究科・臓器再生医学, 大学院生
NAKAZAWA Kenichi  横浜市立大学, 大学院・医学研究科・臓器再生医学, 大学院生
KONDO Akihisa  横浜市立大学, 大学院・医学研究科・臓器再生医学, 大学院生
OTA Mitsuyoshi  横浜市立大学, 附属病院, 准教授
TATSUMI Kenji  横浜市立大学, 医学部, 助教
ICHIKAWA Yasushi  横浜市立大学, 医学研究科, 准教授
ENDO Itaru  横浜市立大学, 医学研究科, 教授
OSHIMA Takashi  横浜市立大学, 市民総合医療センター, 准教授
FUJII Shoichi  横浜市立大学, 市民総合医療センター, 准教授
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords消化器癌 / 幹細胞 / フローサイトメトリー / 腫瘍形成能 / 移植 / 予後予測因子
Research Abstract

Previous reports have demonstrated that CD133^+CD44^+ cells might be putative colorectal cancer stem cells (CSCs). Intestinal stem cell marker is already identified as LGR5 in mice and human. However the correlation of CSCs and normal stem cell are unclear. LGR5 may play a crucial role in the carcinogenesis and tumorigenesis. In this study, we investigated the relation of LGR5 and CSC marker, CD133 and CD44. In vivo subcutaneous transplantation showed that as few as 100 CD133^+CD44^+ cells from primary tumor tissue had tumorigenicity in NOD/SCID mice. In xenograft tumor, LGR5, CD133 and CD44 were over-expressed compared with primary cancer and adjacent normal mucosa. In 167 clinical specimens, LGR5, CD44 or CD133 was expressed strongly compared with normal mucosa (p<0.0001). However, with any single marker was not enough to predict the prognosis. Instead, combined with CD44 or CD133, the group of LGR5 over-expression showed significantly low survival rate (p<0.022). We conclude that LGR5^+, CD133^+ or CD44^+ cells expressed the characters of cancer stem cells in xenograft tumors as well as in primary colorectal cancers. Importantly, LGR5 is a potentially critical factor determining prognosis in clinics.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (66 results)

All 2011 2010 2009 2008 Other

All Journal Article (26 results) (of which Peer Reviewed: 8 results) Presentation (37 results) Book (3 results)

  • [Journal Article] Evidence for mesenchymal-epithelial transition associated with mouse hepatic stem cell differentiation.2011

    • Author(s)
      Li B, Zheng YW, Sano Y, Taniguchi H
    • Journal Title

      PLoS ONE 6(2)

    • Related Report
      2010 Final Research Report
  • [Journal Article] Evidence for mesenchymal-epithelial transition associated with mouse hepatic stem cell differentiation2011

    • Author(s)
      Li B
    • Journal Title

      PLoS ONE

      Volume: 6

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 臨床応用に向けた幹細胞操作法開発における現状と課題2011

    • Author(s)
      谷口英樹
    • Journal Title

      Frontiers in Gastroenterology

      Volume: 16 Pages: 62-71

    • Related Report
      2010 Annual Research Report
  • [Journal Article] EGF signaling activates proliferation and blocks apoptosis of mouse and human intestinal stem/progenitor cells in long-term monolayer cell culture.2010

    • Author(s)
      Suzuki A, Sekiya S, Gunshima E, Fujii S, Taniguchi H
    • Journal Title

      Lab Invest 90(10)

      Pages: 1425-1436

    • Related Report
      2010 Final Research Report
  • [Journal Article] The polycomb group gene product Ezh2 regulates proliferation and differentiation of murine hepatic stem/progenitor cells.2010

    • Author(s)
      Aoki R, Chiba T, Miyagi S, Negishi M, Konuma T, Taniguchi H, Ogawa M, Yokosuka O, Iwama A
    • Journal Title

      J of Hepatology 52

      Pages: 854-863

    • Related Report
      2010 Final Research Report
  • [Journal Article] EGF signaling activates proliferation and blocks apoptosis of mouse and human intestinal stem/progenitor cells in long-term monolayer cell culture2010

    • Author(s)
      Suzuki A
    • Journal Title

      Lab Invest

      Volume: 90 Pages: 1425-36

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human salivary gland stem/progenitor cells remain dormant even after irradiation.2009

    • Author(s)
      Tatsuishi Y, Hirota M, Kishi T, Adachi M, Fukui T, Mitsudo K, Aoki S, Matsui Y, Omura S, Taniguchi H, Tohnai I
    • Journal Title

      International Journal of Molecular Medicine 24(3)

      Pages: 361-366

    • Related Report
      2010 Final Research Report
  • [Journal Article] 消化器官における幹細胞研究はどのようにしてはじまったのか?2009

    • Author(s)
      谷口英樹
    • Journal Title

      分子消化器病(先端医学社) 6(3)

      Pages: 107-113

    • Related Report
      2010 Final Research Report
  • [Journal Article] 大腸幹細胞とニッチ2009

    • Author(s)
      宮田秀俊, 鄭允文, 谷口英樹
    • Journal Title

      再生医療 8(2)

      Pages: 37-44

    • Related Report
      2010 Final Research Report
  • [Journal Article] 肝幹細胞の分離・移植手技2009

    • Author(s)
      鄭允文, 李斌, 谷口英樹
    • Journal Title

      再生医療 8(1)

      Pages: 89-94

    • Related Report
      2010 Final Research Report
  • [Journal Article] Human salivary gland stem/progenitor cells remain dormant even after irradiation2009

    • Author(s)
      Tatsuishi Y
    • Journal Title

      International Journal of Molecular Medicine 24

      Pages: 361-366

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 消化器官における幹細胞研究はどのようにしてはじまったのか?2009

    • Author(s)
      谷口英樹
    • Journal Title

      分子消化器病 6

      Pages: 107-113

    • Related Report
      2009 Annual Research Report
  • [Journal Article] ポリコーム群タンパク質を介した肝幹細胞の自己複製制御2009

    • Author(s)
      上野康晴
    • Journal Title

      生物物理学 53

      Pages: 115-119

    • NAID

      10026143099

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article]2009

    • Author(s)
      谷口英樹, 大島雄二, 喜多清
    • Journal Title

      iPS細胞の糖尿病治療への応用―現状と課題― iPS細胞の産業的応用技術(シーエムシー出版)

      Pages: 202-210

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Flow cytometric isolation and clonal identification of self-renewing bipotent hepatic progenitor cells in adult mouse liver.2008

    • Author(s)
      Suzuki A, Sekiya S, Onishi M, Oshima N, Kiyonari H, Nakauchi H, Taniguchi H
    • Journal Title

      Hepatology 48(6)

      Pages: 1964-1978

    • Related Report
      2010 Final Research Report
  • [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, Aoki R, Seki A, Morita Y, Yonemitsu Y, Yokosuka O, Yaniguchi H, Nakauchi H, Iwama A
    • Journal Title

      Cancer Research 68(19)

      Pages: 7742-7749

    • Related Report
      2010 Final Research Report
  • [Journal Article] Tbx3 controls the fate of hepatic progenitor cells in liver development by suppressing p19ARF expression.2008

    • Author(s)
      Suzuki A, Sekiya S, Buscher D, Izpisua Belmonte JC, Taniguchi H
    • Journal Title

      Development 8135(9)

      Pages: 1589-1595

    • Related Report
      2010 Final Research Report
  • [Journal Article] 固形癌における癌幹細胞の分離・同定2008

    • Author(s)
      宮田秀俊, 鄭允文, 谷口英樹
    • Journal Title

      Organ Biology 15(4)

      Pages: 357-367

    • Related Report
      2010 Final Research Report
  • [Journal Article] 消化器癌における癌幹細胞研究の動向2008

    • Author(s)
      谷口英樹
    • Journal Title

      最新医学 63(12)

      Pages: 97-104

    • Related Report
      2010 Final Research Report
  • [Journal Article] 癌幹細胞(cancer stem cell)研究の動向2008

    • Author(s)
      谷口英樹
    • Journal Title

      BIO EX-press 新緑号

      Pages: 10-14

    • Related Report
      2010 Final Research Report
  • [Journal Article] 消化器領域における組織幹細胞の特性2008

    • Author(s)
      谷口英樹
    • Journal Title

      実験医学 26(5)

      Pages: 204-205

    • Related Report
      2010 Final Research Report
  • [Journal Article] The polycomb gene product BMI1 contributes to the maintenance of tumor-initiating side population cells in hepatocellular carcinoma2008

    • Author(s)
      Chiba T
    • Journal Title

      Cancer Research 68

      Pages: 7742-7749

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 消化器領域における組織幹細胞の特性2008

    • Author(s)
      谷口英樹
    • Journal Title

      実験医学 26

      Pages: 204-205

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 消化器癌における癌幹細胞研究の動向2008

    • Author(s)
      谷口英樹
    • Journal Title

      最新医学 63

      Pages: 97-104

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 固形癌における癌幹細胞の分離・同定2008

    • Author(s)
      宮田 秀俊
    • Journal Title

      Organ Biology 15

      Pages: 357-367

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reconstitution of hepatic tissue architectures from fetal liver cells obtained from a three-dimensional culture with a rotating wall vessel bioreactor.

    • Author(s)
      Ishikawa M, Sekine K, Okamura A, Zheng YW, Ueno Y, Koike N, Tanaka J, Taniguchi H
    • Journal Title

      J Biosci Bioeng in press

    • NAID

      110008672821

    • Related Report
      2010 Final Research Report
  • [Presentation] 前癌細胞(pre-cancerous cell)の増殖制御に基づく肝発癌抑制療法の開発2011

    • Author(s)
      谷口英樹
    • Organizer
      第94回医工学フォーラム
    • Place of Presentation
      京都 招待講演
    • Year and Date
      2011-03-25
    • Related Report
      2010 Final Research Report
  • [Presentation] 再生医療の臨床応用はどこまで進んでいるのか?2011

    • Author(s)
      谷口英樹
    • Organizer
      横浜市港南区医師会創立40周年記念学術講演会
    • Place of Presentation
      横浜 特別講演
    • Year and Date
      2011-02-26
    • Related Report
      2010 Final Research Report
  • [Presentation] Acyclic retinoid inhibits hepatic stem/progenitor cell proliferation and induces cell apoptosis in vitro2011

    • Author(s)
      Yu HW
    • Organizer
      第10回日本再生医療学会総会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] 非環式レチノイドの肝幹/前駆細胞を介した肝発癌抑制作用の検討2011

    • Author(s)
      土田倫範
    • Organizer
      第10回日本再生医療学会総会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト大腸癌におけるCD133+CD44+CD45-CD235a-細胞の腫瘍形成能と局在分析2010

    • Author(s)
      河俣真由美
    • Organizer
      第65回日本消化器外科学会総会
    • Place of Presentation
      山口県下関下関市民会館
    • Year and Date
      2010-07-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] ヒト大腸癌におけるCD133^+CD44^+CD45^-CD235a^-細胞の腫瘍形成能と局在分析2010

    • Author(s)
      河俣真由美
    • Organizer
      第65回日本消化器外科学会総会
    • Place of Presentation
      山口
    • Year and Date
      2010-07-05
    • Related Report
      2010 Final Research Report
  • [Presentation] 消化器領域における癌幹細胞研究の動向2010

    • Author(s)
      谷口英樹
    • Organizer
      第11回九州がん懇話会
    • Place of Presentation
      福岡
    • Year and Date
      2010-04-17
    • Related Report
      2010 Final Research Report
  • [Presentation] 消化器領域における癌幹細胞研究の動向2010

    • Author(s)
      谷口英樹
    • Organizer
      第11回九州がん懇話会
    • Place of Presentation
      福岡県中外製薬福岡支店(招待講演)
    • Year and Date
      2010-04-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] 消化管における幹細胞研究の現状と展望2010

    • Author(s)
      谷口英樹
    • Organizer
      第22回日本小腸移植研究会
    • Place of Presentation
      東京 ランチョンセミナー
    • Year and Date
      2010-03-05
    • Related Report
      2010 Final Research Report
  • [Presentation] 消化管における幹細胞研究の現状と展望2010

    • Author(s)
      谷口英樹
    • Organizer
      第22回日本小腸移植研究会
    • Place of Presentation
      東京
    • Year and Date
      2010-03-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] Mesenchymal epithelial transition is accompanied with mouse hepatic stem cells differentiation2010

    • Author(s)
      李斌
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会
    • Place of Presentation
      神戸 ポスター
    • Related Report
      2010 Final Research Report
  • [Presentation] 化学放射線療法を実施したヒト膵癌組織における膵癌幹細胞マーカーの発現解析2010

    • Author(s)
      生天目明子
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会
    • Place of Presentation
      神戸 ポスター
    • Related Report
      2010 Final Research Report
  • [Presentation] 細胞極性制御因子aPKCλによる上皮前駆細胞の増殖制御とその破綻2010

    • Author(s)
      秋本和憲
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会
    • Place of Presentation
      神戸 ワークショップ
    • Related Report
      2010 Final Research Report
  • [Presentation] Self-renewal versus differentiation in vitro of human hepatic stem cells2010

    • Author(s)
      鄭允文
    • Organizer
      BIT's 3rd Annual world Congress of Regenerative Medicine & Stem Cells
    • Place of Presentation
      Shanghai, China
    • Related Report
      2010 Final Research Report
  • [Presentation] 幹細胞から癌を読み解く-癌幹細胞という概念-2010

    • Author(s)
      谷口英樹
    • Organizer
      日本婦人科腫瘍学会第49回学術講演会
    • Place of Presentation
      佐賀 教育講演
    • Related Report
      2010 Final Research Report
  • [Presentation] Clonal identification and differentiation of human hepatic stem cells.2010

    • Author(s)
      鄭允文
    • Organizer
      8th Annual Meeting of International Society for Stem Cell Research (ISSCR)
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2010 Final Research Report
  • [Presentation] Mesenchymal epithelial transition in the differentiation process of mouse hepatic stem cells.2010

    • Author(s)
      李斌
    • Organizer
      8th Annual Meeting of International Society for Stem Cell Research (ISSCR)
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2010 Final Research Report
  • [Presentation] 幹細胞から癌を読み解く-癌幹細胞という概念-2010

    • Author(s)
      谷口英樹
    • Organizer
      第69回日本癌学会学術集会
    • Place of Presentation
      大阪 癌入門コース1講演
    • Related Report
      2010 Final Research Report
  • [Presentation] 幹細胞研究の形成外科領域への応用2010

    • Author(s)
      谷口英樹
    • Organizer
      第19回日本形成外科学会基礎学術集会
    • Place of Presentation
      横浜 特別講演
    • Related Report
      2010 Final Research Report
  • [Presentation] 非環式レチノイドによる肝発癌抑制作用の検討2010

    • Author(s)
      嶋尾大樹
    • Organizer
      第9回日本再生医療学会総会
    • Place of Presentation
      広島
    • Related Report
      2010 Final Research Report
  • [Presentation] INDUCING FUNCTIONAL HEPATOCYTES FROM HUMAN HEPATIC STEM CELLS WITH A NOVEL CULTURE SYSTEM.2009

    • Author(s)
      李斌
    • Organizer
      The 2nd International Workshop Co-Sponsored by Yokohama City University(YCU) & Center for Biologics Evaluation and Research (CBER), United States Food and Drug Administration (FDA)
    • Place of Presentation
      Yokohama
    • Year and Date
      2009-03-04
    • Related Report
      2010 Final Research Report
  • [Presentation] The current topics on cancer stem cells in solid cancer. Frontier of Cancer Therapy.2009

    • Author(s)
      鄭允文
    • Organizer
      The 1st Joint Seminar of YCU-Texas University MD Anderson Cancer Center.
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      2009-02-15
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト組織幹細胞クローンの産業利用へ向けて2009

    • Author(s)
      谷口英樹
    • Organizer
      第8回ヒューマンサイエンス研究資源バンクセミナー
    • Place of Presentation
      大阪 招待講演
    • Year and Date
      2009-01-27
    • Related Report
      2010 Final Research Report
  • [Presentation] Effects of acyclic retinoid on hepatic progenitor cell in vitro2009

    • Author(s)
      滝口和也
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト大腸癌におけるCD133^+CD44^+細胞の腫瘍形態能と局在解析2009

    • Author(s)
      中澤賢一
    • Organizer
      第68回日本癌学会学術集会
    • Place of Presentation
      横浜(口頭)
    • Related Report
      2010 Final Research Report
  • [Presentation] 個体ベースモデルを用いた腸管陰嚢における細胞増殖分化のシミュレーション(Cell proliferation and differentiation in the intestinal crypt using an individual-based model)2009

    • Author(s)
      加川友己
    • Organizer
      第19回日本数理生物学会年会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] The prospective identification and differentiation of human hepatic stem cells.2009

    • Author(s)
      李斌
    • Organizer
      The 7th Stem Cell Research Sympojium
    • Place of Presentation
      Tokyo
    • Related Report
      2010 Final Research Report
  • [Presentation] Human hepatic stem cell : the porspective isolation and characterization.2009

    • Author(s)
      鄭允文
    • Organizer
      The Okayama 2009 Joint Conference of The 10th International Cell Transplant Congress and The 36th Annual Meeting of The Japan Society for Organ Preservation and Medical Biology (JSOPMB)
    • Place of Presentation
      Okayama
    • Related Report
      2010 Final Research Report
  • [Presentation] 腸管上皮における細胞増殖・分化過程の数理モデリング2009

    • Author(s)
      加川友己
    • Organizer
      日本物理学会第64回年次大会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] BMI1過剰発現によるヒト肝幹細胞から肝細胞への分化2009

    • Author(s)
      李斌
    • Organizer
      第8回日本再生医療学会総会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] フローサイトメトリーを用いたヒト肝幹細胞の分離・同定2009

    • Author(s)
      鄭允文
    • Organizer
      第8回日本再生医療学会総会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト大腸癌における癌幹細胞の分離同定及び特性解析2009

    • Author(s)
      宮田秀俊
    • Organizer
      第8回日本再生医療学会総会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] 結腸陰窩における細胞増殖分化の時空間ダイナミクス2009

    • Author(s)
      堀田徳子
    • Organizer
      第5回「生物数学の理論とその応用」
    • Place of Presentation
      京都
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト大腸癌におけるCD133+CD44+細胞の腫瘍形成能と局在解析2009

    • Author(s)
      中澤賢一
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] 大腸癌における癌幹細胞(cancer stem cell)研究の動向2008

    • Author(s)
      谷口英樹
    • Organizer
      昭和大学横浜市北部病院消化器センターと都築区内科医会との連携勉強会
    • Place of Presentation
      横浜 特別講演
    • Year and Date
      2008-10-27
    • Related Report
      2010 Final Research Report
  • [Presentation] 創薬プロセスの加速化に向けたヒト幹細胞の利用2008

    • Author(s)
      谷口英樹
    • Organizer
      第59回日本電気泳動学会総会 シンポジウム
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] 固形臓器における幹細胞研究の新展開 かわさき2008

    • Author(s)
      谷口英樹
    • Organizer
      サイエンス&テクノロジーフォーラム2008(先端医療セッション)
    • Place of Presentation
      川崎 招待講演
    • Related Report
      2010 Final Research Report
  • [Book] iPS細胞の糖尿病治療への応用-現状と課題-iPS細胞の産業的応用技術2009

    • Author(s)
      谷口英樹, 大島祐二, 喜多清
    • Publisher
      シーエムシー出版
    • Related Report
      2010 Final Research Report
  • [Book] 肝臓 炎症・再生医学事典2009

    • Author(s)
      谷口英樹
    • Publisher
      朝倉書店
    • Related Report
      2010 Final Research Report
  • [Book] 創薬プロセスの加速化に向けたヒト幹細胞の産業利用 幹細胞の分化誘導と応用-ES細胞・iPS細胞・体性幹細胞研究最前線-2009

    • Author(s)
      谷口英樹
    • Publisher
      NTS
    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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