2021 Fiscal Year Final Research Report
Development of novel intervening approaches to cancer progression by comprehensive analyses of interactions between cell adhesion molecules
| Project/Area Number |
20K21539
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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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| Review Section |
Medium-sized Section 50:Oncology and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
伊東 剛 東京大学, 医科学研究所, 助教 (20733075)
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| Project Period (FY) |
2020-07-30 – 2022-03-31
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| Keywords | 免疫グロブリンスーパーファミリータンパク質 / がんの浸潤、転移 / 免疫チェックポイント |
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| Outline of Final Research Achievements |
Immunoglobulin superfamily molecules (IgSFs), one of the largest family proteins in vertebrates, are involved in a variety of cell-cell and cell-substrate interaction. To identify novel bindings of these IgSFs will provide a fundamental knowledge of biological phenomena triggered by cell-cell interaction. The information also leads to novel understanding of various diseases caused by abnormal cell-cell interaction, including tumor invasion/metastasis and tumor immunity. In this study, we obtained following results and outcomes.
1.Comprehensive screening of IgSF interaction of more than 300 molecules was performed by physico-chemical analysis. 2.Key molecules involved in invasion of T-cell lymphomas and in novel immune checkpoints were identified. 3.Functional assays of these key molecules in cell biological approaches or in animal model analysis were performed to obtain promising results to support that these molecules are possible molecular targets for cancer treatment.
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| Free Research Field |
分子腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
IgSF分子間結合は様々な細胞間接着に関わり、その異常はがんの浸潤・転移、腫瘍免疫（免疫チェックポイント）などに関わることが知られている。しかし、IgSF分子間結合は現時点ではゲノム、アミノ酸配列からは予測できず、個々の分子による実験的検証が唯一の解析手法である。本研究では、分子クローニング、ALPHA, SPR 等の物理化学的手法による検索法を確立した。さらにがんの浸潤、転移の鍵分子を同定し、また免疫チェックポインチの新規鍵分子対を同定した。これらは、がんの新規治療の開発にも応用される重要で社会的意義も兼ね備えた研究成果である。
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