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Establishment of oral cancer stem-like cells using normal human tongue keratinocytes

Research Project

Project/Area Number 24792264
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Surgical dentistry
Research InstitutionHyogo Medical University

Principal Investigator

ZUSHI Yusuke  兵庫医科大学, 医学部, 助教 (80581206)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsヒト正常舌角化細胞 / 口腔がん幹細胞 / 国際情報交換
Research Abstract

We newly established human tongue keratinocytes (HTK) cell lines derived from tongue mucosa with retroviral vectors expressing mutant CDK4, cyclinD1, hTERT and dominant negative form of p53. Additional transduction of oncogenic Hras or EGFR together with c-Myc into the HTK-K4DT-DNp53 showed subcutaneous tumor formation in nude mice only around 2 weeks. To determine the frequency of oral cancer initiating cells within these cells, a limiting dilution assay was performed. Orthotopic transplantation of HTK-K4DT-DNp53-Hras-cMyc resulted inlocal growth of tumors in all the mice tested and some of them yielded regional metstastases in 2-3 weeks.We have established an in vitro model for OSCCs with normal human tongue keratinocytes (HTKs) focusing on sequential transduction of defined genetic elements and succeeded in the creation of highly potent cancer initiating cells by introduction of c-MYC and oncogenic Hras on a background of the blockade of the pRB and p53 pathways .

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (17 results)

All 2013 2012 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (11 results)

  • [Journal Article] 口腔扁平上皮癌の発生における Human papillomavirus(HPV) 感染の関与と診断法の検討2013

    • Author(s)
      野口一馬, 寺田友紀, 中野芳郎, 山村倫世, 吉川恭平, 頭司雄介, 森寺邦康, 高岡一樹, 浦出雅裕, 岸本裕充
    • Journal Title

      日本口腔感染症学会雑誌

      Volume: vol.20 No.2 Pages: 70-76

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effect of a nitric oxide synthase inhibitor and a CXC chemokine receptor-4 antagonist on tumor growth and metastasis in a xenotransplanted mouse model of adenoid cystic carcinoma of the oral floor2013

    • Author(s)
      Takaoka K, Zushi Y, Noguchi K, Urade M, et al
    • Journal Title

      Int J Oncol

      Volume: 43(3) Issue: 3 Pages: 737-45

    • DOI

      10.3892/ijo.2013.2011

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional analysis of Zyxin in cell migration and invasive potential of oral squamous cell carcinoma cells.2013

    • Author(s)
      Yamamura M, Noguchi K, Nakano Y, Segawa E at al.
    • Journal Title

      Int J Oncol

      Volume: 42(3) Issue: 3 Pages: 873-80

    • DOI

      10.3892/ijo.2013.1761

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] HPV 陽性および陰性の口腔扁平上皮がんに対する in vitro 多段階発がんモデル2013

    • Author(s)
      頭司雄介, 野口一馬, 浦出雅裕
    • Journal Title

      日本口腔外科学会雑誌

      Volume: vol.59 No.3 Pages: 13-25

    • NAID

      130004707939

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] HPV陽性および陰性の口腔扁平上皮がんに対するin vitro 多段階発がんモデル2013

    • Author(s)
      頭司 雄介, 野口 一馬, 浦出 雅裕
    • Journal Title

      日本口腔外科学会雑誌

      Volume: 59 Pages: 13-25

    • NAID

      130004707939

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HPV陽性および陰性の口腔扁平上皮がんに対するin vitro多段階発がんモデル2013

    • Author(s)
      頭司雄介, 野口一馬, 浦出雅裕
    • Journal Title

      日本口腔外科学会雑誌

      Volume: Vol. 59 No.3 Pages: 13-25

    • NAID

      130004707939

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] in vitro 発癌モデルを用いた口腔発癌におけるドライバー変異の解明2013

    • Author(s)
      野口一馬, 頭司雄介, 吉川恭平, 山村倫世, 吉岡済, 浦出雅裕, 岸本裕充
    • Organizer
      日本口腔組織培養学会設立 50 周年記念学術大会
    • Place of Presentation
      東京
    • Year and Date
      2013-11-23
    • Related Report
      2013 Final Research Report
  • [Presentation] 組織培養を用いた口腔癌研究の最前線-発がんから医療への応用-2013

    • Author(s)
      野口一馬, 頭司雄介, 吉川恭平, 山村倫世, 吉岡済, 浦出雅裕, 岸本裕充
    • Organizer
      日本口腔組織培養学会設立50周年記念学術大会
    • Place of Presentation
      東京
    • Year and Date
      2013-11-23
    • Related Report
      2013 Final Research Report
  • [Presentation] Establishment of oral cancer stem-like cells using normal human tongue keratinocytes2013

    • Author(s)
      Zushi Y, Noguchi K, Yamamura M, Moridera K, Takaoka K, Okui S, Urade M, Kishimoto H
    • Organizer
      54th Congress of the Korean Association of Oral Maxillofacial Surgery (KAOMS2013)
    • Place of Presentation
      Daegu, South Korea
    • Year and Date
      2013-04-26
    • Related Report
      2013 Final Research Report
  • [Presentation] Establishment of oral cancer stem-like cells using normal human tongue keratinocytes2013

    • Author(s)
      Yusuke Zushi,  Kazuma Noguchi, Kuniyasu Moridera, Hiromitsu Kishimoto, Masahiro Urade
    • Organizer
      The 54th Congress of Korean Association of Oral & Maxillofacial Surgery
    • Place of Presentation
      Daegu, Korea
    • Related Report
      2012 Research-status Report
  • [Presentation] 角化囊胞性歯原性腫瘍細胞の細胞株の樹立と病態モデル作成の試み2012

    • Author(s)
      野口一馬, 藤井碧, 頭司雄介, 山村倫世, 吉川恭平, 岸本裕充, 浦出雅裕
    • Organizer
      第49回日本口腔組織培養学会学術大会
    • Place of Presentation
      広島
    • Year and Date
      2012-11-24
    • Related Report
      2013 Final Research Report
  • [Presentation] 当科における口腔扁平上皮癌の臨床的検討- RADPLAT 導入前後の比較-2012

    • Author(s)
      野口一馬, 吉川恭平, 瀬川英美, 川邊睦記, 頭司雄介, 山村倫世, 奥井森, 森寺邦康, 高岡一樹, 岸本裕充, 浦出雅裕
    • Organizer
      第57回日本口腔外科学会総会・学術大会
    • Place of Presentation
      横浜
    • Year and Date
      2012-10-19
    • Related Report
      2013 Final Research Report
  • [Presentation] 病態モデル作成を目指した角化囊胞性歯原性腫瘍細胞の不死化の試みと細胞株の樹立2012

    • Author(s)
      野口一馬, 藤井碧, 頭司雄介, 山村倫世, 吉川恭平, 岸本裕充, 浦出雅裕
    • Organizer
      第57回日本口腔外科学会総会・学術大会
    • Place of Presentation
      横浜
    • Year and Date
      2012-10-19
    • Related Report
      2013 Final Research Report
  • [Presentation] Analysis of carcinogenesis for both HPV-positive and - negative oral squamous cell carcinoma using normal human tongue keratinocytes2012

    • Author(s)
      Zushi Y, Noguchi K, Yoshikawa K, Okui S, Takaoka K, Moridera K, Kishimoto H, Urade M
    • Organizer
      21th Congress of the European Association for Cranio-MaxilloFacial Surgery (EACMFS 2012)
    • Place of Presentation
      Dubrovnik, Croatia
    • Year and Date
      2012-09-12
    • Related Report
      2013 Final Research Report
  • [Presentation] 口腔発がんにおける p53, EGFR, Ras 遺伝子発現の関連性について~ 不死化ヒト正常舌ケラチノサイト(HTK)を用いた解析~2012

    • Author(s)
      頭司雄介, 野口一馬, 吉川恭平, 岸本裕充, 浦出雅裕
    • Organizer
      第66回日本口腔科学会総会
    • Place of Presentation
      広島
    • Year and Date
      2012-05-18
    • Related Report
      2013 Final Research Report
  • [Presentation] Analysis of carcinogenesis for both HPV-positive and –negative oral squamous cell carcinoma using normal human tongue keratinocytes2012

    • Author(s)
      Yusuke Zushi,  Kazuma Noguchi, Kuniyasu Moridera, Hiromitsu Kishimoto, Masahiro Urade
    • Organizer
      21th Congress of the European Association for Cranio-Maxillo- Facial Surgery
    • Place of Presentation
      Dubrovnik, Croatia
    • Related Report
      2012 Research-status Report
  • [Presentation] Establishment of oral cancer stem-like cells using normal human tongue keratinocytes

    • Author(s)
      Yusuke Zushi,  Kazuma Noguchi,  Michiyo Yamamura, Kyohei Yoshikawa,
    • Organizer
      第54回大韓口腔外科学会
    • Place of Presentation
      韓国, 大邱
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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