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Elucidation of molecular mechanisms of a lipid mediator in resistance of breast cancer hormone therapy and its clinical significance

Research Project

Project/Area Number 17K10538
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionNiigata University

Principal Investigator

Ikarashi Mayuko  新潟大学, 医歯学総合病院, 医員 (50790284)

Co-Investigator(Kenkyū-buntansha) 永橋 昌幸  新潟大学, 医歯学総合病院, 研究准教授 (30743918)
土田 純子  新潟大学, 医歯学総合病院, 専任助教 (90769415)
小山 諭  新潟大学, 医歯学系, 教授 (10323966)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords脂質メディエーター / スフィンゴシン-1-リン酸 / 乳癌 / ホルモン療法 / スフィンゴシン‐1-リン酸 / 抗エストロゲン剤耐性株 / スフィンゴシンキナーゼ1型 / スフィンゴシンー1ーリン酸 / スフィンゴシンキナーゼ1型 / スフィンゴシン-1-リン酸 / スフィンゴシン-1-リン酸
Outline of Final Research Achievements

Elucidation and overcoming of resistance mechanism in breast cancer hormone therapy is an important clinical issue. Sphingosine-1-phosphate (S1P) is a lipid mediator that acts as a cell signal transmitter in the same way as a protein, although it is a lipid. The aim of this study was to elucidate the resistance mechanism of hormone therapy through S1P and to establish the research basis for the development of new treatments. In this study, we found that FTY720, which blocks the S1P signaling pathway, suppress the proliferation of hormone therapy-resistant breast cancer cells. In addition, we performed a lipidomics analysis using clinical samples and compared the association with clinicopathologic factors. As a result, we found that high plasma S1P levels are significantly associated with lymph node metastasis in breast cancer patients.

Academic Significance and Societal Importance of the Research Achievements

本研究成果の学術的意義として、(1)脂質メディエータであるS1Pがホルモン療法耐性機序に関与しており、S1Pシグナルを標的とした治療の有効性が実験レベルで明らかになったことと、(2)臨床検体において、S1Pのリンパ節転移との関連が示され、ホルモン陽性乳癌におけるS1Pの重要性が示唆されてことが挙げられる。本研究の成果により、新しいホルモン療法耐性機序に基づいた標的治療薬の開発へつながることが期待される。

Report

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

    (11 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (1 results) Presentation (10 results) (of which Int'l Joint Research: 4 results)

  • [Int'l Joint Research] バージニア州立大学/ロズウェルパーク癌研究所(米国)

    • Related Report
      2019 Annual Research Report
  • [Presentation] Association between estrogen receptor status and plasma S1P levels in breast cancer patients2020

    • Author(s)
      Masayuki Nagahashi, Junko Tsuchida, Mayuko Ikarashi, Kazuki Moro, Chie Toshikawa, Hiroshi Ichikawa, Yoshifumi Shimada, Kazuaki Takabe, Toshifumi Wakai
    • Organizer
      The 15th Annual Academic Surgical Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Involvement of sphingosine-1-phosphate in tumor immune microenvironment of breast cancer patients2020

    • Author(s)
      Junko Tsuchida, Masayuki Nagahashi, Mayuko Ikarashi, Kazuki Moro, Chie Toshikawa, Hiroshi Ichikawa, Yoshifumi Shimada, Kazuaki Takabe, Toshifumi Wakai
    • Organizer
      The 15th Annual Academic Surgical Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 乳癌患者における血漿中スフィンゴシン-1-リン酸濃度の臨床的意義2019

    • Author(s)
      五十嵐 麻由子,永橋 昌幸,土田 純子,遠藤 麻巳子,諸 和樹,庭野 稔之,山浦 久美子,利川 千絵,長谷川 美樹,中島 真人,小山 諭,若井 俊文
    • Organizer
      第27回日本乳癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Sphingosine-1-phospate signaling regulates drug resistance mediated by glutathione2019

    • Author(s)
      Nagahashi M, Tsuchida J, Moro K, Ikarashi M, Nakajima M, Abe M, Saito T, Komatsu M, Soga T, Takabe K, Sakimura K, Wakai T
    • Organizer
      The 14th Annual Academic Surgical Congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Levels of sphingolipids in plasma are elevated in breast cancer patients with lymph node metastasis2019

    • Author(s)
      Junko Tsuchida, Masayuki Nagahashi, Kazuki Moro, Mayuko Ikarashi, Yu Koyama, Jun Sakata, Takashi Kobayashi, Hitoshi Kameyama, Kazuaki Takabe, Toshifumi Wakai
    • Organizer
      The 14th Annual Academic Surgical Congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Obesity-induced sphingosine-1-phosphate in tumor interstitial fluid promotes angiogenesis and breast cancer progression2018

    • Author(s)
      Nagahashi M, Tsuchida J, Moro K, Yuza K, Hirose Y, Ikarashi M, Sakata J, Kobayashi T, Kameyama H, Wakai T, Takabe K
    • Organizer
      第15回臨床腫瘍学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 乳癌細胞の代謝動態におけるスフィンゴシン-1-リン酸産生酵素の働き2017

    • Author(s)
      永橋昌幸,中島真人,土田純子,諸 和樹,遠藤麻巳子,大渓彩香,庭野稔之,辰田久美子,長谷川美樹,利川千絵,五十嵐麻由子,坂田 純,亀山仁史,小林 隆,高部和明,斎藤哲也,小松雅明,曽我朋義,小山 諭,若井俊文
    • Organizer
      第24回外科侵襲とサイトカイン研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] 乳がんのがん細胞と宿主におけるスフィンゴシン-1-リン酸産生酵素の機能解析2017

    • Author(s)
      中島 真人,永橋 昌幸,大谷 彩香,遠藤 麻已子,土田 純子,諸 和樹,庭野 稔之,山浦 久美子,利川 千絵,長谷川 美樹,五十嵐 麻由子,小山 諭,坂田 純,亀山 仁史,小林 隆,若井 俊文
    • Organizer
      第25回日本乳癌学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] シンポジウム15 私たちが日本で行うべき乳癌研究 基礎から臨床まで 日本だからこそできるトランスレーショナルリサーチの実践を目指して2017

    • Author(s)
      永橋 昌幸,大渓 彩香,遠藤 麻巳子,土田 純子,諸 和樹,庭野 稔之,辰田 久美子,利川 千絵,長谷川 美樹,五十嵐 麻由子,中島 真人,小山 諭,高部 和明,若井 俊文
    • Organizer
      第25回日本乳癌学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Sphingosine-1-phosphate affects tumor-associated immune cells in human breast cancer patients2017

    • Author(s)
      Tsuchida J, Nagahashi M, Moro K, Otani A, Endo M, Ikarashi M, Nakajima M, Koyama Y, Sakata J, Kobayashi T, Kameyama H, Yan Q, Yan L, Takabe K, Wakai T
    • Organizer
      The 13th Annual Academic Surgical Congress
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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