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Analysis of biological characteristic features in cancer stem cell in digestive organs

Research Project

Project/Area Number 20590809
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKeio University

Principal Investigator

HIGUCHI Hajime  Keio University, 医学部, 助教 (20306682)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords癌幹細胞 / epithelial-to-mesenchymal transition / apoptosis / mesenchymal stem cell / アポトーシス / EMT / side population / Spheroid / FMT
Research Abstract

Cancer related materials, i.e., cell lines, endoscopic biopthy specimen, or, surgically resected specimen, were analyzed for ; i) expression of cancer stem cell markers, ii) tumor formation, iii) colony forming activity, iv) drug-resistance, and v) potentials for local invasion and metastasis. Our results suggest that side population (SP) cells isolated from pancreatic cancer have some cancer stem cell-like properties ; i) high tumorigenic/colony forming activity, ii) resistance to some chemotherapeutic drugs as well as apoptosis-inducing molecules such as TRAIL, iii) high metstatic potential, and iv) enhanced capability to undergo epithelial-to-mesenchymal transition (EMT) and invasion. In hepatocellular carcinoma, CD133-positive side population cells were highly tumorigenic and chemotherapy-resistant. These cancer stem cell-like features were enhanced by co-culturing with bone marrow-derived mesenchymal stem cells (MSCs) and/or MSC-derived myofibroblast-like cells, suggesting MSCs provide microenvironment so-called cancer stem cell niche to maintain stem cell phenotype in cancer derived SP cells. These results suggest that SP cells would be a therapeutic tagrget, especially to prevent cancer sten cell invasion and metastasis. Mesenchymal cell-derived microenvironment would be another terapeutic target to regulate cancer stem cell maintenance.

Report

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

    (11 results)

All 2010 2009 2008 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (5 results) Remarks (1 results)

  • [Journal Article]2010

    • Author(s)
      Satoshi Kurita, Hajime Higuchi, Yoshimasa Saito, Nobuhiro Nakamoto, Hiromasa Takaishi, Shinichiro Tada, Hidetsugu Saito, Gregory J. Gores, Toshifumi Hibi
    • Journal Title

      Cancer Sci 101

      Pages: 1431-1439

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNMT1 and DNMT3b silencing sensitizes human hepatoma cells to TRAIL-mediated apoptosis via up-regulation of TRAIL-R2/DR5 and caspase-82010

    • Author(s)
      Kurita S, et al.
    • Journal Title

      Cancer Science

      Volume: 101 Pages: 1431-1439

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Side population of pancreatic cancer cells predominates in TGF-beta-mediated epithelial to mesenchymal transition and invasion.2009

    • Author(s)
      Ayano Kabashima, Hajime Higuchi, Hiromasa Takaishi, Yumi Matsuzaki, Sadafumi Suzuki, Motoko Izumiya, Hideko Iizuka, Gen Sakai, Shigenari Hozawa, Toshifumi Azuma, Toshifumi Hibi
    • Journal Title

      Int-J-Cancer 124

      Pages: 2771-2779

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Side population of pancreatic cancer cells predominates in TGF-beta-me diated epithelial to mesenchymal transition and invasion2009

    • Author(s)
      Kabashima A, et al.
    • Journal Title

      International Journal of Cancer 124

      Pages: 2771-2779

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Side population of pancreatic cancer cells predominates in TGF-beta-mediated epithelial to mesenchymal transition and invasion.2009

    • Author(s)
      Kabashima A, Higuchi H, Takaishi H, Matsuzaki Y, Suzuki S, Tzumiya M, Sakai G, Hozawa S, Azuma T, Hibi T
    • Journal Title

      Tnt J Cancer 124

      Pages: 2771-2779

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Wnt signaling contributes to the maintenance of cancer stem cell-like populations in Huh7 hepatocellular carcinoma cell line : Role of hepatic stellate cells.2010

    • Author(s)
      Masayuki Adachi, Hajime Higuchi, Ayano Kabashima, Shinsuke Funakoshi, Shoko Nakamura, Hiromasa Takaishi, Toshifumi Hibi
    • Organizer
      AACR meeting abstract 2010, 203
    • Place of Presentation
      Washington
    • Related Report
      2010 Final Research Report
  • [Presentation] Cancer stem cell like properties of 5-fluorouracil resistant Panc2010

    • Author(s)
      Motoko Izumiya, Hajime Higuchi, Ayano Kabashima, Toru Igarashi, Shoko Nakamura, Shinsuke Funakoshi, Masayuki Adachi, Hiromasa Takaishi, Toshifumi Hibi
    • Organizer
      AACR meeting abstract 2010, 335 101^<st> American Association for Cancer Research
    • Place of Presentation
      Washington
    • Related Report
      2010 Final Research Report
  • [Presentation] Mesenchymal stem cells induce epithelial-to-mesenchymal transition (EMT) in metastatic SP cells in pancreatic cancer.2010

    • Author(s)
      Ayano Kabashima, Hajime Higuchi, Yumi Matsuzaki, Shinsuke Funakoshi, Masayuki Adachi, Motoko Izumiya, Gen Sakai, Toru Igarashi, Shoko Nakamura, Hiromasa Takaishi, Toshifumi Hibi
    • Organizer
      AACR meeting abstract 2010, 387 101st American Association for Cancer Research
    • Place of Presentation
      Washington
    • Related Report
      2010 Final Research Report
  • [Presentation] Isolation and identification of Notch signal positive cells in pancreatic cancer cell line.2009

    • Author(s)
      Gen Sakai, Hajime Higuchi, Hiromasa Takaishi, Motoko Izumiya, Masaya Adachi, Ayano Kabashima, Shouko Nakamura, Toshifumi Hibi
    • Organizer
      AACR meeting abstract 2009, 193 100^<th> American Association for Cancer Research.
    • Place of Presentation
      Denver
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト膵癌細胞株由来side population細胞はTGF-betaによる浸潤・FMTへ高井反応性を持つ.2008

    • Author(s)
      樺嶋彩乃, 樋口肇, 松崎有未, 泉谷幹子, 飯塚秀子, 酒井元, 高石官均, 日比紀文
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-28
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

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

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