| Project/Area Number |
17K19503
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pharmaceutical Sciences and related fields
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
Kanda Yasunari 国立医薬品食品衛生研究所, 薬理部, 部長 (70510387)
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 乳癌 / 脂質 / 幹細胞 / 自己複製 / 増殖機構 / ALDH / 癌幹細胞 / リゾリン脂質 / リゾホスファチジン酸 / 受容体 / 創薬 / 発生・分化 / シグナル伝達 / トランスレーショナルリサーチ |
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| Outline of Final Research Achievements |
Breast cancer is the leading cause of cancer death in women worldwide. Especially, there are no available targeted therapies against triple-negative (TN) type of breast cancer, due to lack of hormone receptors and HER2 amplification. Growing evidence suggests that breast cancers originate from breast cancer stem cells (BCSCs), which is a minor population of cells that display stem cell properties. Here, using lipid screening in BCSC model, we have identified a role for a lipid mediator Lysophosphatidic acid (LPA) in TN-type CSC expansion. By using deep sequencing data, we identified IL-8 as a downstream signaling for BCSC regulation. We have currently performed lipidomics using BCSCs and found several lipids which are enriched in BCSCs. Taken together, our findings provide new insights into the lipid-mediated regulation of TN-type BCSCs.
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| Academic Significance and Societal Importance of the Research Achievements |
乳癌は女性で罹患数・死亡数ともに最も高いがんであり、近年の治療法の進歩にも関わらず、いまだ乳癌の再発や転移を克服できておらず、医学的にも社会的にも大きな問題である。乳癌の中でもトリプルネガティブタイプは予後が悪いが、有効な分子治療薬がない。本研究で我々はトリプルネガティブタイプの乳癌の新たな標的として、脂質の一種であるLPAシグナルを見出した。さらに、乳癌のもととなる癌幹細胞に発現量が多い他の脂質の同定にも成功している。これらの成果をもとに、乳癌に対する新たな創薬の標的分子が明らかとなり、治療法の開発につながることが期待される。
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