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Antitumor effect of LAT1 inhibition on clear cell sarcoma

Research Project

Project/Area Number 18K16623
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionKobe University

Principal Investigator

Morishita Masayuki  神戸大学, 医学研究科, 医学研究員 (30814321)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords明細胞肉腫 / LAT1 / アポトーシス / LAT1阻害剤 / オートファジー / 代謝 / LAT-1 / AMPK
Outline of Final Research Achievements

L-type amino acid transporter 1 (LAT1) is expressed in various malignancies and plays an important role in the uptake of essential amino acids. Meanwhile, herein, the therapeutic potential of targeting LAT1 was investigated using a human clear cell sarcoma cell line in which LAT1 is highly expressed. In the human clear cell sarcoma cell line MP-CCS-SY, JPH203, a selective LAT1 inhibitor, decreased the cellular uptake of essential amino acids, such as leucine; in combination with doxorubicin, it inhibited cell growth and promoted apoptosis. This study suggests that LAT1 could be a useful therapeutic target for clear cell sarcoma for which no standard drug therapy exists. JPH203 administration is expected to have an add-on effect on conventional anticancer drugs. This is a very useful achievement and is of great social significance for clear cell sarcoma, a rare cancer for which it is difficult to develop new treatments.

Academic Significance and Societal Importance of the Research Achievements

明細胞肉腫においてLAT1の高発現に着目した治療はこれまでに報告がない。本研究によりLAT1の選択的阻害が明細胞肉腫の治療において新たな知見を得た。LAT1の選択的阻害が、既存のドキソルビシンなどの抗がん剤に併用することで治療効果の増強につながる可能性が示唆された。LAT1選択的阻害剤JPH203は他の癌腫での治験において人体に安全に投与可能であることが報告されており、明細胞肉腫においても従来の抗がん剤への「上乗せ効果」が期待される。新規治療開発が困難な希少癌である明細胞肉腫において非常に有用な成果であり、社会的意義も高いものである。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (4 results)

All 2022 2020 2019

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

  • [Presentation] 明細胞肉腫薬物治療におけるLAT1阻害剤による増感効果の検討2022

    • Author(s)
      森下雅之, 藤本卓也, 河本旭哉, 須藤保, 藤田郁夫,藤田昌秀,黒田良祐,秋末敏宏
    • Organizer
      第55回日本整形外科学会骨・軟部腫瘍学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Anti-tumor effect of LAT1 inhibitor in clear cell sarcoma2020

    • Author(s)
      森下 雅之
    • Organizer
      25th CTOS virtual Annual Meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 明細胞肉腫に対する LAT1 阻害剤の抗腫瘍効果の検討2019

    • Author(s)
      森下 雅之
    • Organizer
      第52回日本整形外科学会骨・軟部腫瘍学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 明細胞肉腫に対するLAT1阻害剤の抗腫瘍効果の検討2019

    • Author(s)
      森下雅之,藤本卓也,河本旭哉,秋末敏宏,藤田郁夫,重本理花,竹森俊幸,藤原周一,北山和道,川上洋平,深瀬直政,原仁美,須藤保,黒田良祐
    • Organizer
      第2回日本サルコーマ治療研究学会学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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