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Signal integration by CD30 through HSP90 in classical Hodgkin lymphoma

Research Project

Project/Area Number 26460440
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionKitasato University

Principal Investigator

Horie Ryouichi  北里大学, 医療衛生学部, 教授 (80229228)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsホジキンリンパ腫 / HSP90 / CD30 / 未分化大細胞型リンパ腫 / ALK / シグナル伝達 / Hodgkin リンパ腫 / Hodgkinリンパ腫
Outline of Final Research Achievements

Although classical Hodgkin lymphoma (cHL) cells bear deregulation of multiple signaling pathways, the mechanisms of how these pathways are integrated are not fully understood. We show involvement of CD30 in this process. CD30 facilitates phosphorylation of heat shock protein factor (HSF)1 and induces heat shock protein (HSP) 90 via JNK. CD30 repression and subsequent inhibition of HSP90 suppresses NF-κB, ERK/MAPK, AKT, and STAT pathways in cHL cell lines. Thus CD30 mediated induction of HSP90 appears to serve as a central hub for integration of intracellular signaling in cHL cells. Although anaplastic large cell lymphoma (ALCL) is associated with CD30 overexpression, our experiments reveal that HSP90 induction in ALCL bearing NPM- ALK does not depend on CD30 but instead on ALK via JNK. Together these results highlight a novel role for CD30 in mediating integration of signaling pathways of cHL cells while being replaced in this function by ALK in ALCL cells.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (12 results)

All 2017 2016 2015 2014

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Acknowledgement Compliant: 3 results) Presentation (6 results) (of which Invited: 1 results) Book (1 results)

  • [Journal Article] CD30 induces heat shock protein 90 and signal integration in classic Hodgkin lymphoma cells2017

    • Author(s)
      Watanabe M, Nakano K, Kadin ME, Higashihara M, Watanabe T, Horie R
    • Journal Title

      Am J Pathol

      Volume: 187 Issue: 1 Pages: 163-175

    • DOI

      10.1016/j.ajpath.2016.09.007

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Sucsessful treatment with ibrutinib of intractable thrombocytopenia associated with recurrent chronic lymphocytic leukemia2017

    • Author(s)
      Ishida T, Yokoyama M, Danbara M, Michisita Y, Horie R, Higashihara M, Miyazaki K
    • Journal Title

      The Kitasato Medical Journal

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immature platelet fraction measurement is influenced by platelet size and is a useful parameter for discrimination of macrothrombocytopenia2015

    • Author(s)
      Miyazaki K, Koike Y, Kunishima S, Ishii R, Danbara M, Horie R, Yatomi Y, Higashihara M
    • Journal Title

      Hematology

      Volume: 20 Issue: 10 Pages: 587-592

    • DOI

      10.1179/1607845415y.0000000021

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Brefeldin A exerts differential effects on anaplastic lymphoma kinase positive anaplastic large cell lymphoma and Hodgkin lymphoma cell lines.2015

    • Author(s)
      T. Toda, M. Watanabe, J. Kawato, M. Higashihara, T. Kunisada, K. Umezawa and R. Horie
    • Journal Title

      British J. Haematology

      Volume: 170 Issue: 6 Pages: 837-846

    • DOI

      10.1111/bjh.13508

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Brefeldin A exerts differential effects on anaplastic lymphoma kinase positive anaplastic large cell lymphoma and classical Hodgkin lymphoma cell lines2015

    • Author(s)
      Toda T, Watanabe M, Kawato J, Kadin ME, Higashihara M, Kunisada T, Umezawa K, and Horie R
    • Journal Title

      Br J Haematol

      Volume: in press

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] The emergence of hyperploid cells in CD30+ subpopulation of adult T-cell leukemia2016

    • Author(s)
      Makoto Nakashima, Tadanori Yamochi, Mariko Watanabe, Atae Utsunomia, Masaaki Higashihara, Kaoru Uchimaru, Toshiki Watanabe, Ryouichi Horie
    • Organizer
      第78回日本血液学会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] 古典的Hodgkinリンパ腫におけるCD30を介したHSP90誘導とシグナル統合機構の解析2016

    • Author(s)
      堀江良一、渡邉真理子、内丸薫、中野和民、Marshall E. Kadin、渡邉俊樹、東原正明
    • Organizer
      第56回日本リンパ網内系学会
    • Place of Presentation
      ホテル日航熊本 (熊本県熊本市 ) (誌上発表)
    • Year and Date
      2016-09-01
    • Related Report
      2016 Annual Research Report
  • [Presentation] 成人T細胞性白血病におけるCD30陽性集団に高倍数体細胞は出現する2016

    • Author(s)
      中島誠、矢持忠徳、渡邉真理子、内丸薫、宇都宮與、東原正明、渡邉俊樹、堀江良一
    • Organizer
      第3回日本HTLV-1学会学術集会
    • Place of Presentation
      鹿児島県市町村自治会館(鹿児島県鹿児島市 )
    • Year and Date
      2016-08-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] Differential effects of Brefeldin A on anaplastic large cell lymphoma and Hodgkin lymphoma2015

    • Author(s)
      堀江良一、戸田崇史、渡邉真理子、河戸淳仁、Marshall E. Kadin、梅澤一夫、東原正明
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      石川県立音楽堂他(石川県・金沢市)
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
  • [Presentation] ALK陽性未分化大細胞型リンパ腫と古典的Hodgkinリンパ腫細胞株に対して異なる感受性を示す薬剤の探索とBrefeldin Aの同定2015

    • Author(s)
      堀江良一、戸田崇史、渡邉真理子、河戸淳仁、梅澤一夫、東原正明
    • Organizer
      第55回日本リンパ網内系学会総会
    • Place of Presentation
      岡山コンベンションセンター(岡山県・岡山市)
    • Year and Date
      2015-07-09
    • Related Report
      2015 Research-status Report
  • [Presentation] Hodgkinリンパ腫細胞の分化と癌幹細胞. シンポジウムIII 「Hodgkinリンパ腫の分子機構の解明と新たな治療戦略」2014

    • Author(s)
      堀江 良一
    • Organizer
      第54回日本リンパ網内系学会総会
    • Place of Presentation
      山形国際ホテル(山形)
    • Year and Date
      2014-06-20
    • Related Report
      2014 Research-status Report
    • Invited
  • [Book] 特集 ホジキンリンパ腫2016

    • Author(s)
      堀江良一
    • Total Pages
      148
    • Publisher
      医薬ジャーナル
    • Related Report
      2015 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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