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Analysis of cancer stem cells related to metastasis and recurrence in hepatocellular carcinoma

Research Project

Project/Area Number 24659610
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionYamaguchi University

Principal Investigator

OKA MASAAKI  山口大学, 医学(系)研究科(研究院), 教授 (70144946)

Co-Investigator(Kenkyū-buntansha) TSUNEDOMI Ryouichi  山口大学, 大学院医学系研究科, 助教 (10420514)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords肝癌 / 癌幹細胞 / 肝細胞癌
Research Abstract

The possible existence of plasticity between cancer stem cells and their more differentiated derivative cancer cells was suggested. We successfully induced cancer stem-like sphere cells from human HCC cell lines with specified medium. Poorly differentiated HCC derived SK-HEP-1 and undifferentiated HCC derived HLE cell lines efficiently formed spheres (SK-sphere and HLE-sphere). In the presence of several anti-cancer drugs except sorafenib, the cell viability of SK-sphere and HLE-sphere were significantly higher than that of parental cells. SK-sphere showed higher HIF1A mRNA expression, more CD44 variant-positive cells, and lower ROS production compared to parental cells. Integrated analysis showed that HIF1A and its downstream genes were up-regulated in SK-sphere. Finally, e identified several new marker and therapy target candidates (mRNA, microRNA, and protein) to cancer stem cells by integrated omics analysis.

Report

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

    (42 results)

All 2013 2012 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (36 results)

  • [Journal Article] ABCB6 mRNA and DNA methylation levels serve as useful biomarkers for prediction of early intrahepatic recurrence of hepatitis C virus-related hepatocellular carcinoma2013

    • Author(s)
      Ryouichi Tsunedomi, Masaaki Oka, 他8名
    • Journal Title

      International Journal of Oncology

      Volume: 42巻 Pages: 1551-1559

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Susceptibility of hepatoma-derived cells to histone deacetylase inhibitors is associated with ID2 expression2013

    • Author(s)
      Ryouichi Tsunedomi, Masaaki Oka, 他2名
    • Journal Title

      International Journal of Oncology

      Volume: 42巻 Pages: 1159-1166

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] ABCB6 mRNA and DNA methylation levels serve as useful biomarkers for prediction of early intrahepatic recurrence of hepatitis C virus-related hepatocellular carcinoma.2013

    • Author(s)
      Ryouichi Tsunedomi, Norio Iizuka, Kiyoshi Yoshimura, Michihisa Iida, Masahito Tsutsui, Noriaki Hashimoto, Shinsuke Kanekiyo, Kazuhiko Sakamoto, Takao Tamesa, and Masaaki Oka.
    • Journal Title

      International Journal of Oncology

      Volume: 42 Issue: 5 Pages: 1555-1559

    • DOI

      10.3892/ijo.2013.1854

    • Related Report
      2013 Annual Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Susceptibility of hepatoma-derived cells to histone deacetylase inhibitors is associated with ID2 expression.2013

    • Author(s)
      Ryouichi Tsunedomi, Norio Iizuka, Sawako Harada, and Masaaki Oka.
    • Journal Title

      International Journal of Oncology

      Volume: 42 Issue: 4 Pages: 1159-1166

    • DOI

      10.3892/ijo.2013.1811

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of the RD RNA binding protein in hepatitis C virus-related hepatocellular carcinoma2012

    • Author(s)
      Michihisa Iida, Ryouichi Tsunedomi, Masaaki Oka, 他8名
    • Journal Title

      Oncology Reports

      Volume: 28巻 Pages: 728-734

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of the RD RNA binding protein in hepatitis C virus-related hepatocellular carcinoma.2012

    • Author(s)
      Iida M
    • Journal Title

      Oncol Rep

      Volume: 28 Issue: 2 Pages: 728-734

    • DOI

      10.3892/or.2012.1821

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] CANCER-STEM CELL-LIKE SPHERE CELLS INDUCED FROM A CELL LINE DERIVED FROM POORLY-DIFFERENTIATED HEPATOCELLULAR CARCINOMA EXERTS LIVER METASTATIC POTENTIAL AND CHEMORESISTANCE2013

    • Author(s)
      Ryouichi Tsunedomi
    • Organizer
      21st United European Gastroenterology Week (UEGW2013)
    • Place of Presentation
      ICC Berlin, (Berlin, The Federal Republic of GERMANY)
    • Year and Date
      2013-10-16
    • Related Report
      2013 Final Research Report
  • [Presentation] 肝細胞癌におけるMCM6の発現とその意義2013

    • Author(s)
      飯田通久
    • Organizer
      第21回日本消化器関連学会週間(JDDW2013)
    • Place of Presentation
      グランドプリンスホテル新高輪(東京)
    • Year and Date
      2013-10-11
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒト膵癌細胞株を用いた癌幹細胞が豊富な細胞集団の誘導2013

    • Author(s)
      吉村清
    • Organizer
      第21回日本消化器関連学会週間(JDDW2013)
    • Place of Presentation
      グランドプリンスホテル新高輪(東京)
    • Year and Date
      2013-10-11
    • Related Report
      2013 Final Research Report
  • [Presentation] 抗癌剤耐性を示すヒト肝細胞癌細胞株から誘導した癌幹細胞様細胞2013

    • Author(s)
      恒富亮一
    • Organizer
      第21回日本消化器関連学会週間(JDDW2013)
    • Place of Presentation
      グランドプリンスホテル新高輪(東京)
    • Year and Date
      2013-10-11
    • Related Report
      2013 Final Research Report
  • [Presentation] prediction for early intrahepatic recurrence after hepatectomy in patient with HCC based on serum methylation signature2013

    • Author(s)
      Shinsuke Kanekiyo
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2013-10-05
    • Related Report
      2013 Final Research Report
  • [Presentation] Overexpression of MCM6 is associated with poor prognosis of hepatocellular carcinoma2013

    • Author(s)
      Michihisa Iida
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2013-10-05
    • Related Report
      2013 Final Research Report
  • [Presentation] Chemoresistance of induced cancer-stem cell-like sphere cells from a human hepatocellular carcinoma cell line2013

    • Author(s)
      Ryouichi Tsunedomi
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2013-10-04
    • Related Report
      2013 Final Research Report
  • [Presentation] Cancer stem like cells induced from human pancreatic cancer cell lines have epithelial-mesenchymal transition property2013

    • Author(s)
      Yusaku Watanabe
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2013-10-03
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒト肝細胞癌細胞株から誘導した癌幹細胞様細胞の抗癌剤耐性2013

    • Author(s)
      恒富亮一
    • Organizer
      第24回日本消化器癌発生学会総会
    • Place of Presentation
      金沢音楽堂(石川)
    • Year and Date
      2013-09-06
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒト膵癌幹細胞からの癌幹細胞の培養による誘導2013

    • Author(s)
      吉村清
    • Organizer
      第17回日本がん免疫学会総会
    • Place of Presentation
      ANAクラウンプラザホテル宇部(山口)
    • Year and Date
      2013-07-05
    • Related Report
      2013 Final Research Report
  • [Presentation] 低分化型肝細胞癌株から誘導された癌幹細胞様細胞の解析2013

    • Author(s)
      橋本憲輝
    • Organizer
      第17回日本がん免疫学会総会
    • Place of Presentation
      ANAクラウンプラザホテル宇部(山口)
    • Year and Date
      2013-07-04
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒト膵癌幹細胞を用いた癌幹細胞richな細胞集団の誘導とその培養液中のサイトカインの検索2013

    • Author(s)
      渡邊裕策
    • Organizer
      第17回日本がん免疫学会総会
    • Place of Presentation
      ANAクラウンプラザホテル宇部(山口)
    • Year and Date
      2013-07-04
    • Related Report
      2013 Final Research Report
  • [Presentation] HCV陽性肝細胞癌におけるMCM6発現の意義2013

    • Author(s)
      飯田通久
    • Organizer
      第113回日本外科学会定期学術集会
    • Place of Presentation
      マリンメッセ福岡(福岡)
    • Year and Date
      2013-04-11
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒト膵癌幹細胞における微?周辺環境の探索2013

    • Author(s)
      吉村清
    • Organizer
      第113回日本外科学会定期学術集会
    • Place of Presentation
      福岡サンパレス(福岡)
    • Year and Date
      2013-04-11
    • Related Report
      2013 Final Research Report
  • [Presentation] 2つのトランスクリプトーム解析からのHCV関連肝細胞癌予後予測2013

    • Author(s)
      恒富亮一
    • Organizer
      第113回日本外科学会定期学術集会
    • Place of Presentation
      マリンメッセ福岡(福岡)
    • Year and Date
      2013-04-11
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒト膵癌細胞株からのCancer Stem Cellsの誘導2012

    • Author(s)
      吉村清
    • Organizer
      第25回日本バイオセラピィ学会学術集会総会
    • Place of Presentation
      倉敷市芸文館(岡山)
    • Year and Date
      2012-12-13
    • Related Report
      2013 Final Research Report
  • [Presentation] 肝細胞癌術後肝内再発予測マーカーとしてのABCB6遺伝子2012

    • Author(s)
      恒富亮一
    • Organizer
      第23回日本消化器癌発生学会総会
    • Place of Presentation
      ルネッサンスリゾートナルト(徳島)
    • Year and Date
      2012-11-16
    • Related Report
      2013 Final Research Report
  • [Presentation] 肝細胞癌におけるMCM6の発現解析2012

    • Author(s)
      飯田通久
    • Organizer
      第23回日本消化器癌発生学会総会
    • Place of Presentation
      ルネッサンスリゾートナルト(徳島)
    • Year and Date
      2012-11-15
    • Related Report
      2013 Final Research Report
  • [Presentation] RELIABLE PREDICTION OF EARLY INTRAHEPATIC RECURRENCE OF HCV-RELATED HEPATOCELLULAR CARCINOMA AFETR SURGERY BY GENE EXPRESSIONAL PROFILING2012

    • Author(s)
      Ryouichi Tsunedomi
    • Organizer
      20th United European Gastroenterology Week (UEGW2012)
    • Place of Presentation
      RAI国際会議場(Amsterdam, THE NETHERLANDS)
    • Year and Date
      2012-10-22
    • Related Report
      2013 Final Research Report
  • [Presentation] HCV関連肝細胞癌における予後予測2012

    • Author(s)
      恒富亮一
    • Organizer
      第20回日本消化器関連学会週間(JDDW2012)
    • Place of Presentation
      神戸国際展示場(神戸)
    • Year and Date
      2012-10-12
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒト低分化型肝細胞癌株からの癌幹細胞の誘導の試み2012

    • Author(s)
      吉村清
    • Organizer
      第20回日本消化器関連学会週間(JDDW2012)
    • Place of Presentation
      ポートピアホテル(神戸)
    • Year and Date
      2012-10-11
    • Related Report
      2013 Final Research Report
  • [Presentation] Cancer-stem cell-like sphere cells induced from a cell line derived from poorly-differentiated hepatocellular carcinoma2012

    • Author(s)
      Ryouichi Tsunedomi
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市教育文化会館(札幌)
    • Year and Date
      2012-09-19
    • Related Report
      2013 Final Research Report
  • [Presentation] Inducing pancreatic cancer stem cell like population by culture and the analysis of its microenvironment2012

    • Author(s)
      Kiyoshi Yoshimura
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市教育文化会館(札幌)
    • Year and Date
      2012-09-19
    • Related Report
      2013 Final Research Report
  • [Presentation] 培養による膵癌幹細胞Richポピュレーションの誘導時の微小周辺環境の探索2012

    • Author(s)
      吉村清
    • Organizer
      第16回日本がん免疫学会総会
    • Place of Presentation
      北海道大学学術交流会館(札幌)
    • Year and Date
      2012-07-27
    • Related Report
      2013 Final Research Report
  • [Presentation] 血清を用いたCpG island methylator phenotype (CIMP)による予後評価への応用2012

    • Author(s)
      飯田通久
    • Organizer
      第112回日本外科学会定期学術集会
    • Place of Presentation
      幕張メッセ(千葉)
    • Year and Date
      2012-04-13
    • Related Report
      2013 Final Research Report
  • [Presentation] CANCER-STEM CELL-LIKE SPHERE CELLS INDUCED FROM A CELL LINE DERIVED FROM POORLY-DIFFERENTIATED HEPATOCELLULAR CARCINOMA EXERTS LIVER METASTATIC POTENTIAL AND CHEMORESISTANCE

    • Author(s)
      Ryouichi Tsunedomi
    • Organizer
      21st United European Gastroenterology Week
    • Place of Presentation
      Berlin, The Federal Republic of GERMANY
    • Related Report
      2013 Annual Research Report
  • [Presentation] 抗癌剤耐性を示すヒト肝細胞癌細胞株から誘導した癌幹細胞様細胞

    • Author(s)
      恒富 亮一
    • Organizer
      第21回日本消化器関連学会週間 (JDDW2013)
    • Place of Presentation
      グランドプリンスホテル新高輪、東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Chemoresistance of induced cancer-stem cell-like sphere cells from a human hepatocellular carcinoma cell line

    • Author(s)
      Ryouichi Tsunedomi
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜 、横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] ヒト肝細胞癌細胞株から誘導した癌幹細胞様細胞の抗癌剤耐性

    • Author(s)
      恒富 亮一
    • Organizer
      第24回日本消化器癌発生学会総会
    • Place of Presentation
      石川県立音楽堂 、金沢
    • Related Report
      2013 Annual Research Report
  • [Presentation] 2つのトランスクリプトーム解析からのHCV関連肝細胞癌予後予測

    • Author(s)
      恒富 亮一
    • Organizer
      第113回日本外科学会定期学術集会
    • Place of Presentation
      マリンメッセ福岡 、福岡
    • Related Report
      2013 Annual Research Report
  • [Presentation] 肝細胞癌におけるMCM6の発現とその意義

    • Author(s)
      飯田通久
    • Organizer
      第67回日本消化器外科学会総会
    • Place of Presentation
      富山国際会議場 ・富山
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒト低分化型肝細胞癌株からの癌幹細胞の誘導の試み

    • Author(s)
      吉村 清
    • Organizer
      第20回日本消化器関連学会集会
    • Place of Presentation
      ポートピアホテル・神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] HCV関連肝細胞癌における予後予測

    • Author(s)
      恒富亮一
    • Organizer
      第20回日本消化器関連学会集会
    • Place of Presentation
      ポートピアホテル・神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] 低分化型幹細胞癌由来細胞株から誘導した癌幹細胞様Sphere細胞

    • Author(s)
      恒富亮一
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      ロイトン札幌・札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] 肝細胞癌後肝内再発予測マーカーとしてのABCB6遺伝子

    • Author(s)
      恒富亮一
    • Organizer
      第23回日本消化器癌発生学会総会
    • Place of Presentation
      ルネッサンスリゾートナルト・鳴門
    • Related Report
      2012 Research-status Report
  • [Presentation] 肝細胞癌におけるMCM6の発現解析

    • Author(s)
      飯田通久
    • Organizer
      第23回日本消化器癌発生学会総会
    • Place of Presentation
      ルネッサンスリゾートナルト・鳴門
    • Related Report
      2012 Research-status Report

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

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