| Project/Area Number |
18K09285
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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| Research Institution | Shinshu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
竹内 穂高 信州大学, 医学部附属病院, 助教(診療) (30816351)
鹿島 大靖 信州大学, 学術研究院医学系(医学部附属病院), 講師 (70464089)
山田 靖 信州大学, 学術研究院医学系(医学部附属病院), 助教 (60646652)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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)
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| Keywords | LCN2 / 癌幹細胞性 / 鉄運搬タンパク / 酸化ストレス耐性 / CD44v / 合成LCN2 / Lipocalin2 / 抗がん剤耐性 / Sphere形成能 / CD44 / CD133 / 鉄運搬 / salinomycin / 子宮内膜癌 / 卵巣明細胞癌 / 鉄イオン |
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| Outline of Final Research Achievements |
This study aimed to elucidate the effects and molecular mechanisms of LCN2 on the maintenance of cancer stemness in gynecological cancer cells. In several gynecological cancer cell lines, the expression of cancer stem cell markers CD44v and CD133 was decreased by suppressing LCN2 expression and was restored by the addition of synthetic LCN2 (sLCN2). In addition, the number of colonies with anchorage-independent growth on soft agar, an indicator of stemness, was significantly decreased by suppression of LCN2 expression and recovered by the addition of sLCN2. Flow cytometry also showed that LCN2 suppression reduced the percentage of side population cells that contained most of the cancer stem cells. These results indicate that LCN2 acts to maintain cancer stemness.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果はLCN2の幹細胞性維持に対する作用を示している。一方、LCN2は鉄輸送に係る因子であるが、鉄イオンと幹細胞性維持の関連を示す論文も複数存在している。一般に癌幹細胞では酸化ストレス耐性や抗癌剤耐性が増強しているとされており、我々も本研究やこれまでの研究でLCN2の作用として示してきた。これまでLCN2を標的とした高悪性腫瘍治療は開発されておらず、新規性が高い。また本研究成果は癌幹細胞を標的とした新規治療法につながる可能性がある。
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