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2011 Fiscal Year Final Research Report

Investigation of the roles of tumor environment in osteosarcoma

Research Project

  • PDF
Project/Area Number 22700887
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Tumor biology
Research InstitutionKeio University

Principal Investigator

SHIMIZU Takatsune  慶應義塾大学, 医学部, 特任助教 (40407101)

Project Period (FY) 2010 – 2011
Keywords癌 / 環境
Research Abstract

The roles of environmental soluble factors in the formation of histopathological characteristics of osteosarcoma(OS) remains to be elucidated. Here, a newly established murine OS model was used to clarify the roles of environmental factors such as fibroblast growth factor-2(Fgf2) or leukemia inhibitory factor(Lif) in the maintenance of OS cells in an immature state. These factors were highly expressed in stromal fibroblasts and macrophages, but not in OS cells, and potently suppressed osteogenesis of OS cells in vitro and in vivo. Further investigations revealed that the activation of Erk1/2 induced by these factors was deeply involved in the process of OS differentiation. In addition, Fgf2 enhanced both proliferation and migratory activity of OS cells and modulated the sensitivity to an anti-cancer drug. These findings suggest that the seemingly chaotic structures of OS could be dependent on the distribution of such factors. The combined blockade of the signaling pathways of several growth factors, including Fgf2, might be useful in controlling the aggressiveness of OS.

  • Research Products

    (7 results)

All 2012 2011 2010 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (2 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Fibroblast growth factor-2 is an important factor that maintains cellular immaturity and contributes to aggressiveness of osteosarcoma2012

    • Author(s)
      Shimizu T, Ishikawa T, Iwai S, Ueki A, Sugihara E, Onishi N, Kuninaka S, Miyamoto T, Toyama Y, Ijiri H, Mori H, Matsuzaki Y, Yaguchi T, Nishio H, Kawakami Y, Ikeda Y, Saya H
    • Journal Title

      Mol. Cancer Res.

      Volume: 10 Pages: 454-468

    • Peer Reviewed
  • [Journal Article] Establishment of a choriocarcinoma model from immortalized normal extravillous trophoblast cells transduced with HRASV122011

    • Author(s)
      Kobayashi Y, Shimizu T, Naoe H, Ueki A, Ishizawa J, Chiyoda T, Onishi N, Sugihara E, Nagano O, Banno K, Kuninaka S, Aoki D, Saya H
    • Journal Title

      Am. J. Pathol

      Volume: 179 Pages: 1471-82

    • Peer Reviewed
  • [Journal Article] c-MYC overexpression with loss of Ink4a/Arf transforms bone marrow stromal cells into osteosarcoma accompanied by loss of adipogenesis2010

    • Author(s)
      Shimizu T, Ishikawa T, Sugihara E, Kuninaka S, Miyamoto T, Mabuchi Y, Matsuzaki Y, Tsunoda T, Miya F, Morioka H, Nakayama R, Kobayashi E, Toyama Y, Kawai A, Ichikawa H, Hasegawa T, Okada S, Ito T, Ikeda Y, Suda T, Saya H
    • Journal Title

      Oncogene

      Volume: 29 Pages: 5687-99

    • Peer Reviewed
  • [Presentation] Multifunctional roles of Fibroblast growth factor-2(Fgf2) in the histopathology of murine osteosarcoma2011

    • Author(s)
      清水孝恒
    • Organizer
      第70回日本癌学会学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-04
  • [Presentation] Mesenchymal differentiation potentials modify osteosarcoma stem cell activities2010

    • Author(s)
      清水孝恒
    • Organizer
      American Association for cancer research 101^<st> Annual meeting 2010
    • Place of Presentation
      Washington, U. S. A.
    • Year and Date
      2010-04-21
  • [Book] がん幹細胞研究の動向と治療標的としての将来性.最新医学(特集:がん幹細胞と支持細胞を標的とする薬剤の開発)2011

    • Author(s)
      清水孝恒, 吉田剛, 佐谷秀行
    • Total Pages
      387-392
  • [Remarks]

    • URL

      http://www.genereg.jp/

URL: 

Published: 2013-07-31  

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