• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of a novel therapeutic modality against both cancerous and inflammatory diseases based on the understanding of the characteristics of mesothelial cells

Research Project

Project/Area Number 17K19628
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Tumor biology and related fields
Research InstitutionAichi Cancer Center Research Institute

Principal Investigator

Sekido Yoshitaka  愛知県がんセンター(研究所), 分子腫瘍学分野, 副所長兼分野長 (00311712)

Co-Investigator(Kenkyū-buntansha) 佐藤 龍洋  愛知県がんセンター(研究所), 分子腫瘍学分野, 主任研究員 (70547893)
Project Period (FY) 2017-06-30 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords中皮細胞 / 細胞増殖 / 上皮間葉転換 / アノイキス / 3次元培養 / シグナル伝達系 / 遺伝子発現 / 細胞特性 / 癌 / 中皮 / 炎症 / 分子標的
Outline of Final Research Achievements

Mesothelial cells show different cellular characteristics comparing to epithelial cells. Mesothelial cells play important roles on cancer and inflammation, but the study of mesothelial cells is lagging behind. In this study, we focused on anoikis resistance and epithelial-to-mesenchymal transition. We employed several immortalized mesothelial cell lines which we established and performed comprehensive mRNA expression analysis, phospho-receptor tyrosine kinase array, and three dimensional culture. We found that the immortalized mesothelial cells with epithelial morphology showed a characteristic gene expression profile, phosphorylation status of the receptor tyrosine kinases, and sensitivity to anoikis. We also obtained unique findings of these immortalized mesothelial cell lines. These results strongly indicated that a new therapeutic strategy might be developed toward diseases which are associated with activated mesothelial cells.

Academic Significance and Societal Importance of the Research Achievements

中皮細胞は胸膜・腹膜の表面を覆い、主に臓器間の潤滑な移動・摩擦の軽減といった役割を担う。しかし、中皮細胞は他にも様々な役割を有することが明らかとなり、活性化した中皮細胞はがんや炎症の主座や支持組織として、病態の悪性化や重症化に結び付くことが示唆されている。一方、中皮細胞の研究は極めて遅れており、その本態についてはほとんど明らかになっていない。本研究成果により、中皮細胞のアノイキス抵抗性や上皮間葉転換に関してその特性の一端が明らかとなった。本研究を今後さらに継続・発展させることにより、中皮細胞の増殖・活性化が基盤となる疾患の新規治療法の開発に応用可能であることが強く示唆された。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (38 results)

All 2020 2019 2018 2017 Other

All Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 10 results) Presentation (25 results) (of which Int'l Joint Research: 5 results,  Invited: 10 results) Remarks (2 results)

  • [Journal Article] Frequent homozygous deletion of Cdkn2a/2b in tremolite‐induced malignant mesothelioma in rats2020

    • Author(s)
      Okazaki Yasumasa、Misawa Nobuaki、Akatsuka Shinya、Kohyama Norihiko、Sekido Yoshitaka、Takahashi Takashi、Toyokuni Shinya
    • Journal Title

      Cancer Science

      Volume: N/A Issue: 4 Pages: 1180-1192

    • DOI

      10.1111/cas.14358

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Carbonic anhydrase 9 confers resistance to ferroptosis/apoptosis in malignant mesothelioma under hypoxia2019

    • Author(s)
      Li Zan、Jiang Li、Chew Shan Hwu、Hirayama Tasuku、Sekido Yoshitaka、Toyokuni Shinya
    • Journal Title

      Redox Biology

      Volume: 26 Pages: 101297-101297

    • DOI

      10.1016/j.redox.2019.101297

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Progress of malignant mesothelioma research in basic science: A review of the 14th international conference of the international mesothelioma interest group (iMig2018).2019

    • Author(s)
      Wu L, Dell'Anno I, Lapidot M, Sekido Y, Chan ML, Kohno M, Serre-Beinier V, Felley-Bosco E, de Perrot M.
    • Journal Title

      Lung Cancer

      Volume: 127 Pages: 138-145

    • DOI

      10.1016/j.lungcan.2018.11.034

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TAZ activation by Hippo pathway dysregulation induces cytokine gene expression and promotes mesothelial cell transformation.2019

    • Author(s)
      Matsushita A, Sato T, Mukai S, Fujishita T, Mishiro-Sato E, Okuda M, Aoki M, Hasegawa Y, Sekido Y
    • Journal Title

      Oncogene

      Volume: 38 Issue: 11 Pages: 1966-1978

    • DOI

      10.1038/s41388-018-0417-7

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Integrative Molecular Characterization of Malignant Pleural Mesothelioma2018

    • Author(s)
      Hmeljak Julija、TCGA Research Network et al (他58名、48番目)
    • Journal Title

      Cancer Discovery

      Volume: 8 Issue: 12 Pages: 1548-1565

    • DOI

      10.1158/2159-8290.cd-18-0804

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Connective tissue growth factor-specific monoclonal antibody inhibits growth of malignant mesothelioma in an orthotopic mouse model.2018

    • Author(s)
      Ohara Y, Chew SH, Misawa N, Wang S, Somiya D, Nakamura K, Kajiyama H, Kikkawa F, Tsuyuki Y, Jiang L, Yamashita K, Sekido Y, Lipson KE, Toyokuni S.
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 26 Pages: 18494-18509

    • DOI

      10.18632/oncotarget.24892

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] State of the Art: Advances in Malignant Pleural Mesothelioma in 20172018

    • Author(s)
      McCambridge Amanda J.、Napolitano Andrea、Mansfield Aaron S.、Fennell Dean A.、Sekido Yoshitaka、Nowak Anna K.、Reungwetwattana Thanyanan、Mao Weimin、Pass Harvey I.、Carbone Michele、Yang Haining、Peikert Tobias
    • Journal Title

      J Thorac Oncol

      Volume: S1556 Issue: 5 Pages: 30175-8

    • DOI

      10.1016/j.jtho.2018.02.021

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Targeting the Hippo Pathway Is a New Potential Therapeutic Modality for Malignant Mesothelioma2018

    • Author(s)
      Sekido Yoshitaka
    • Journal Title

      Cancers

      Volume: 10 Issue: 4 Pages: 90-90

    • DOI

      10.3390/cancers10040090

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] NF2/Merlin Inactivation and Potential Therapeutic Targets in Mesothelioma2018

    • Author(s)
      Sato Tatsuhiro、Sekido Yoshitaka
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 19 Issue: 4 Pages: 988-988

    • DOI

      10.3390/ijms19040988

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of Hippo pathway transcription factor TEAD by p38 MAPK-induced cytoplasmic translocation2017

    • Author(s)
      Lin Kimberly C.、Moroishi Toshiro、Meng Zhipeng、Jeong Han-Sol、Plouffe Steven W.、Sekido Yoshitaka、Han Jiahuai、Park Hyun Woo、Guan Kun-Liang
    • Journal Title

      Nature Cell Biology

      Volume: 19 Issue: 8 Pages: 996-1002

    • DOI

      10.1038/ncb3581

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hyaluronic acid enhances cell migration and invasion via the YAP1/TAZ-RHAMM axis in malignant pleural mesothelioma2017

    • Author(s)
      Shigeeda W, Shibazaki M, Yasuhira S, Masuda T, Tanita T, Kaneko Y, Sato T, Sekido Y, Maesawa C.
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 55 Pages: 93729-93740

    • DOI

      10.18632/oncotarget.20750

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 悪性中皮腫細胞株の樹立:遺伝子異常の本態解析から臨床応用を目指して2019

    • Author(s)
      1.関戸好孝
    • Organizer
      日本組織培養学会 第92回大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 悪性中皮腫におけるHippo経路のターゲッティング2019

    • Author(s)
      関戸好孝
    • Organizer
      2019 World Conference on Lung Cancer
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 中皮腫におけるmTORシグナル伝達経路の活性化と新規治療標的因子の探索2019

    • Author(s)
      佐藤龍洋、関戸好孝
    • Organizer
      第1回日本石綿・中皮腫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] O-GlcNAc修飾は悪性中皮腫の腫瘍進展を促進する2019

    • Author(s)
      向井智美、佐藤龍洋、三城(佐藤)恵美、青木正博、藪田紀一、関戸好孝
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 悪性中皮腫の遺伝子変異2019

    • Author(s)
      関戸好孝
    • Organizer
      藤田学園医学会第51回総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] SmgGDSによるRheb-mTORC1シグナル伝達制御と悪性中皮種がん化への関与2019

    • Author(s)
      佐藤龍洋、向井智美、関戸好孝
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 悪性中皮腫における基礎研究の進歩2019

    • Author(s)
      関戸好孝
    • Organizer
      第60回日本肺癌学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] TAZ Activation by NF2-Hippo Pathway Dysregulation Induces Cytkine Expression and Provides Growth Advantage to Mesothelioma2018

    • Author(s)
      関戸好孝
    • Organizer
      iMig2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] IL-1受容体拮抗薬はHippo経路の破綻した悪性中皮腫細胞の進展を抑制する2018

    • Author(s)
      向井智美、松下明弘、佐藤龍洋、藤下晃章、青木正博、関戸好孝
    • Organizer
      第22回日本がん分子標的治療学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 悪性中皮腫におけるRheb-SmgGDS-mTORシグナル伝達経路の解析2018

    • Author(s)
      佐藤龍洋、向井智美、関戸好孝
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 悪性中皮腫においてLATS2はO-GlcNAc化を抑制する2018

    • Author(s)
      向井智美、佐藤龍洋、三城(佐藤)恵美、青木正博、薮田紀一、関戸好孝
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 悪性中皮腫におけるBAP1遺伝子変異に対する合成致死遺伝子の網羅的探索2018

    • Author(s)
      村上優子、清成信一、田部陽子、門松健治、三井田孝博、関戸好孝
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 255症例の悪性胸膜中皮腫の網羅的遺伝子解析2018

    • Author(s)
      竹下純平、辰野健二、松本大地、栗林康造、近藤展行、長谷川誠紀、佐藤鮎子、辻村亨、大多茂樹、河上祐、中野孝司、関戸好孝、油谷浩幸
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 悪性中皮腫におけるBAP1遺伝子変異に対する合成致死遺伝子の網羅的探索2018

    • Author(s)
      村上優子、天野美希、小木曽杏奈、清成信一、紅朋浩、田部陽子、金田典雄、門松健治、三井田孝博、村上浩士、関戸好孝
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 悪性中皮腫におけるHippo経路の破綻による腫瘍進展機構2018

    • Author(s)
      向井智美、松下明弘、佐藤龍洋、藤下晃章、三城恵美、奥田真帆、青木正博、関戸好孝
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 悪性中皮腫の遺伝子異常とその特性2018

    • Author(s)
      関戸好孝
    • Organizer
      中皮腫シンポジウム 悪性中皮腫の診断/治療の最前線
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 悪性中皮腫の遺伝子異常と細胞特性2018

    • Author(s)
      関戸好孝
    • Organizer
      日本薬学会東海支部特別講演会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 243症例の悪性胸膜中皮腫の統合的ゲノム解析2017

    • Author(s)
      竹下純平、山本尚吾、辰野健二、白石友一、大搗泰一郎、栗林康造、近藤展行、長谷川誠紀、佐藤鮎子、辻村亨、中野孝司、関戸好孝、油谷浩幸
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 転写共役因子TAZは、IL-1bの転写活性を介して悪性中皮腫の進展を促進する2017

    • Author(s)
      向井智美、松下明弘、佐藤龍洋、藤下晃章、青木正博、関戸好孝
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Merlinを発現しない中皮腫において、FAK阻害剤への抵抗性はE-cadherin発現量と相関する2017

    • Author(s)
      佐藤龍洋、加藤毅人、関戸好孝
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Merlin陰性悪性中皮腫においてE-cadherinの発現はVS-4718の耐性と相関する2017

    • Author(s)
      加藤毅人、横井香平、関戸好孝
    • Organizer
      第58回日本肺癌学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Transcriptional co-activator TAZ enhances malignant phenotypes of mesothelioma cells.2017

    • Author(s)
      松下明弘、長谷川好規、関戸好孝
    • Organizer
      第58回日本肺癌学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] New Biological Insights.2017

    • Author(s)
      Sekido Y
    • Organizer
      第18回世界肺癌学会議
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Mesothelioma: Bench to Bedside2017

    • Author(s)
      Sekido Y
    • Organizer
      第18回世界肺癌学会議
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Transcriptional coactivator TAZ enhances malignant phenotypes of mesothelioma cells.2017

    • Author(s)
      Sekido Y, Matsushita A, Mukai S, Sato T.
    • Organizer
      EMBOワークショップ
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Remarks] 分子腫瘍学分野 研究紹介(専門家向け) 悪性中皮腫におけるHippoシグナル伝達系異常の解明

    • URL

      https://www.pref.aichi.jp/cancer-center/ri/01bumon/03bunshi_shuyo/02kenkyu_senmon.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 分子腫瘍学分野 研究テーマ紹介

    • URL

      http://www.pref.aichi.jp/cancer-center/ri/01bumon/03bunshi_shuyo/02kenkyu_senmon.html

    • Related Report
      2018 Research-status Report

URL: 

Published: 2017-07-21   Modified: 2021-02-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi