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Roles of LPA receptors in the acquisition of malignant properties in cancer cells treated with anticancer drugs

Research Project

Project/Area Number 18K07249
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionKindai University

Principal Investigator

Tsujiuchi Toshifumi  近畿大学, 理工学部, 教授 (10254492)

Co-Investigator(Kenkyū-buntansha) 朴木 寛弥  奈良県立医科大学, 医学部, 教授 (40336863)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsリゾフォスファチジン酸 / LPA受容体 / がん細胞 / 抗がん剤 / 抗がん剤抵抗性 / LPA / リゾフォスファチジン酸(LPA) / 抗がん剤耐性 / ABCトランスポーター
Outline of Final Research Achievements

Lysophosphatidic acid (LPA) is a simple lipid and mediates various biological responses through the binding of G protein-coupled LPA receptors. Six subtypes of LPA receptors (LPA1) to LPA6) have been identified so far. It is considered that LPA receptor signaling is involved in the pathogenesis of human diseases, including cancer. In this study, we investigated the roles of LPA receptor signaling in the cellular functions induced by anticancer drug treatment in cancer cells. Our results have shown that the individual LPA receptors regulate cell motility, invasion and metastasis in cancer cells treated with anticancer drugs. Moreover, the activation of LPA receptor-mediated signaling promotes the modulation of anticancer drug resistance in cancer cells. Therefore, it is suggested that LPA receptor signaling is a potent pharmacological target for the establishment of effective chemotherapeutic agents.

Academic Significance and Societal Importance of the Research Achievements

本研究により、抗がん剤処理によって生じる様々ながん細胞の生物学的特性の変化にLPA受容体シグナルが促進または抑制的に作用することが明らかとなった。特に、抗がん剤に対する細胞生存率の制御にLPA受容体シグナルが関与することは、がん薬物療法を困難とさせる抗がん剤抵抗性を獲得したがん症例に対する効果的ながん薬物療法開発のための有用な情報源である。広範囲な浸潤や遠隔臓器への転移をきたした症例に対して、がん薬物療法は限られた選択肢のひとつであり、本研究を基盤とする新規分子標的療法の開発はこれからのがん治療成績向上にむけて大きな可能性のひとつを示したものである。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (23 results)

All 2021 2020 2019 2018

All Journal Article (14 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 14 results) Presentation (9 results)

  • [Journal Article] Roles of endothelial cells in the regulation of cell motility via lysophosphatidic acid receptor-2 (LPA2) and LPA3 in osteosarcoma cells2021

    • Author(s)
      Minami Kanako、Ueda Nanami、Ishimoto Kaichi、Kurisu Rio、Takamoto Miyu、Ikeda Hiroko、Tsujiuchi Toshifumi
    • Journal Title

      Experimental and Molecular Pathology

      Volume: 118 Pages: 104596-104596

    • DOI

      10.1016/j.yexmp.2020.104596

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lysophosphatidic acid receptor-2 (LPA2)-mediated signaling enhances chemoresistance in melanoma cells treated with anticancer drugs.2020

    • Author(s)
      Minami K, Ueda N, Ishimoto K, Tsujiuchi T.
    • Journal Title

      Mol Cell Biochem

      Volume: 469 Issue: 1-2 Pages: 89-95

    • DOI

      10.1007/s11010-020-03730-w

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Different effects of lysophosphatidic acid receptor-2 (LPA2) and LPA5 on the regulation of chemoresistance in colon cancer cells.2020

    • Author(s)
      Ishimoto K, Minami A, Minami K, Ueda N, Tsujiuchi T.
    • Journal Title

      J Recept Signal Transduct Res

      Volume: 16 Issue: 1 Pages: 1-6

    • DOI

      10.1080/10799893.2020.1794002

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cooperation of G12/13 and Gi proteins via lysophosphatidic acid receptor-2 (LPA2) signaling enhances cancer cell survival to cisplatin.2020

    • Author(s)
      Minami K, Ueda N, Ishimoto K, Kurisu R, Takamoto M, Ikeda H, Tsujiuchi T.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 532 Issue: 3 Pages: 427-432

    • DOI

      10.1016/j.bbrc.2020.08.087

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LPA5-mediated signaling induced by endothelial cells and anticancer drug regulates cellular functions of osteosarcoma cells2020

    • Author(s)
      Minami Kanako、Ueda Nanami、Ishimoto Kaichi、Tsujiuchi Toshifumi
    • Journal Title

      Experimental Cell Research

      Volume: 388 Issue: 1 Pages: 111813-111813

    • DOI

      10.1016/j.yexcr.2020.111813

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulation of cell survival through free fatty acid receptor 1 (FFA1) and FFA4 induced by endothelial cells in osteosarcoma cells2020

    • Author(s)
      Minami Kanako、Ueda Nanami、Ishimoto Kaichi、Tsujiuchi Toshifumi
    • Journal Title

      Journal of Receptors and Signal Transduction

      Volume: 40 Issue: 2 Pages: 181-186

    • DOI

      10.1080/10799893.2020.1725047

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of lysophosphatidic acid (LPA) receptor-2 (LPA2) and LPA3 on the regulation of chemoresistance to anticancer drug in lung cancer cells2020

    • Author(s)
      Ueda Nanami、Minami Kanako、Ishimoto Kaichi、Tsujiuchi Toshifumi
    • Journal Title

      Cellular Signalling

      Volume: 69 Pages: 109551-109551

    • DOI

      10.1016/j.cellsig.2020.109551

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Modulation of chemoresistance by lysophosphatidic acid (LPA) signaling through LPA5 in melanoma cells treated with anticancer drugs2019

    • Author(s)
      Minami Kanako、Ueda Nanami、Maeda Haruka、Ishimoto Kaichi、Otagaki Shiho、Tsujiuchi Toshifumi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 517 Issue: 2 Pages: 359-363

    • DOI

      10.1016/j.bbrc.2019.07.092

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rapid establishment of highly migratory cells from cancer cells for investigating cellular functions2019

    • Author(s)
      Ishimoto Kaichi、Minami Kanako、Otagaki Shiho、Tsujiuchi Toshifumi
    • Journal Title

      Journal of Receptors and Signal Transduction

      Volume: 39 Issue: 3 Pages: 194-198

    • DOI

      10.1080/10799893.2019.1638399

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of LPA signaling via LPA receptor-2 in the promotion of malignant properties in osteosarcoma cells2018

    • Author(s)
      Takahashi K, Fukushima K, Tanaka K, Minami K, Ishimoto K, Otagaki S, Fukushima N, Honoki K, Tsujiuchi T
    • Journal Title

      Exp Cell Res.

      Volume: 369 Issue: 2 Pages: 316-324

    • DOI

      10.1016/j.yexcr.2018.05.037

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Involvement of FFA1 and FFA4 in the regulation of cellular functions during tumor progression in colon cancer cells.2018

    • Author(s)
      Takahashi K, Fukushima K, Onishi Y, Minami K, Otagaki S, Ishimoto K, Fukushima N, Honoki K, Tsujiuchi T.
    • Journal Title

      Exp Cell Res.

      Volume: 369 Issue: 1 Pages: 54-54

    • DOI

      10.1016/j.yexcr.2018.05.005

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Lysophosphatidic acid receptor-2 (LPA2) and LPA5 regulate cellular functions during tumor progression in fibrosarcoma HT1080 cells.2018

    • Author(s)
      Takahashi K, Minami K, Otagaki S, Ishimoto K, Fukushima K, Fukushima N, Honoki K, Tsujiuchi T.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 503 Issue: 4 Pages: 2698-2698

    • DOI

      10.1016/j.bbrc.2018.08.026

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Induction of GPR40 positively regulates cell motile and growth activities in breast cancer MCF-7 cells.2018

    • Author(s)
      Fukushima K, Takahashi K, Kusaka M, Ishimoto K, Otagaki S,Minami K, Fukushima N, Honoki K, Tsujiuchi T.
    • Journal Title

      J Recept Signal Transduct Res.

      Volume: 38 Issue: 4 Pages: 311-311

    • DOI

      10.1080/10799893.2018.1494742

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Promotion of cell invasive activity through the induction of LPA receptor-1 in pancreatic cancer cells.2018

    • Author(s)
      Fukushima K, Otagaki S,Takahashi K, Minami K, Ishimoto K, Fukushima N, Honoki K, Tsujiuchi T.
    • Journal Title

      J Recept Signal Transduct Res.

      Volume: 38 Issue: 4 Pages: 367-367

    • DOI

      10.1080/10799893.2018.1531889

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Lysophosphatidic acid (LPA) signaling via LPA receptors regulates chemoresistance of lung cancer cells.2020

    • Author(s)
      Ueda N, Minami K, Ishimoto K, Ikeda H, Tsujiuchi T.
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Involvement of LPA receptor-mediated signaling in the regulation of chemoresistance in colon cancer cells.2020

    • Author(s)
      Ishimoto K, Minami K, Ueda N, Ikeda H, Tsujiuchi T.
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Roles of LPA2-mediated signaling in the acquisition of chemoresistance of fibrosarcoma cells.2020

    • Author(s)
      Minami K, Ueda N, Ishimoto K, Ikeda H, Honoki K, Tsujiuchi T.
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 抗がん剤処理線維肉腫細胞の細胞機能の制御におけるリゾフォスファチジン酸受容体-2(LPA2)およびLPA5の効果2019

    • Author(s)
      南加奈子、石本海智、上田七海、太田垣志帆、朴木寛弥、辻内俊文
    • Organizer
      第78回日本癌学会学術総会(京都)
    • Related Report
      2019 Research-status Report
  • [Presentation] 長期抗がん剤処理大腸がん細胞の生物学的機能の変化におけるLPA受容体の役割2019

    • Author(s)
      石本海智、南加奈子、上田七海、太田垣志帆、朴木寛弥、辻内俊文
    • Organizer
      第78回日本癌学会学術総会(京都)
    • Related Report
      2019 Research-status Report
  • [Presentation] 高運動肺がん細胞の細胞機能調節におけるLPA1およびLPA2の抑制効果2019

    • Author(s)
      上田七海、南加奈子、石本海智、太田垣志帆、朴木寛弥、辻内俊文
    • Organizer
      第78回日本癌学会学術総会(京都)
    • Related Report
      2019 Research-status Report
  • [Presentation] Effects of LPA receptors on the acquisition of malignant properties in colon cancer cells treated with anticancer drug.2018

    • Author(s)
      K. Ishimoto, S. Otagaki, K. Minami, K. Honoki, T. Tsujiuchi.
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Involvement of lysophosphatidic acid receptors in the promotion of malignant properties in pancreatic cancer cells.2018

    • Author(s)
      S. Otagaki, K. Minami, K. Ishimoto, K. Honoki, T. Tsujiuchi.
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Roles of lysophosphatidic acid receptors in cellular functions by anticancer drug treatment in fibrosarcoma cells.2018

    • Author(s)
      K. Minami, K. Ishimoto, S. Otagaki, K. Honoki, T. Tsujiuchi.
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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