| Project/Area Number |
18H02675
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Waseda University |
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Principal Investigator |
Maruyama Takeshi 早稲田大学, 高等研究所, 講師(任期付) (30613872)
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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 |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2020: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
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| Keywords | がん / 上皮細胞 / がん変異細胞 / がんの予防的治療 / 細胞競合 / 抗原提示 / 抗原提示変化 / がん変異細胞排除 / 上皮細胞間相互作用 / 同種細胞間認識 / ゲノム編集 |
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| Outline of Final Research Achievements |
Epithelial cells in the early stage of carcinogenesis with mutations in the proto-oncogene Ras are outcompeted to the lumenal side (out of the body) by surrounding normal cells (cell competition phenomenon). However, it has been unclear how normal cells recognize Ras-transformed cells. Recently, we found that the normal cell protein receptor ECAR elicits an antitumor response by recognizing MHC-I, which is upregulated in RasV12 cells.
Starting from the time of aberration, normal epithelial cells are able to, a) Sensing the physical properties of RasV12 cells and priming them (induction of ECAR expression), b) Recognition of MHC-I of RasV12 cells by the induced ECAR, and then c) Induction of exclusion of RasV12 cells We have shown that this is a multi-step mechanism.
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| Academic Significance and Societal Importance of the Research Achievements |
抗原提示による上皮細胞の抗腫瘍の制御機構を医療に応用することで、まさに「発がんする前にがん変異細胞を除去する」という超早期がんの治療を対象とした「予防的医療」へと発展できると期待される。これまで臨床対象になってこなかった超早期がん治療法の確立のために、病変部位（あるいはその存在）を診断するバイオマーカーの開発、および「正常上皮細胞によるがん細胞の排除を促進する」という全く新規の作用メカニズムを標的としたがん治療薬の開発が必須となる。正常細胞が変異細胞を「認識」し、自身の抗腫瘍能を惹起するメカニズムの解明は、まさに新規薬剤の開発に繋がるため、国内外におけるインパクトは非常に大きい。
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