Development of novel intervening approaches to cancer progression by comprehensive analyses of interactions between cell adhesion molecules
| Project/Area Number |
20K21539
|
|---|
| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Medium-sized Section 50:Oncology and related fields
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
伊東 剛 東京大学, 医科学研究所, 助教 (20733075)
|
|---|
| Project Period (FY) |
2020-07-30 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
|
|---|
| 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 / がん浸潤・転移 / 分子間結合 / 糖鎖 / 腫瘍免疫 |
|---|
| Outline of Research at the Start |
炎症・免疫、感染、がん転移等を細胞接着の異常と捉え、鍵となる分子相互作用を同定するために、時空間的相互作用の多様性に富む免疫グロブリン・スーパーファミリー (IgSF) 分子群を標的とクローニングし、細胞外ドメインの物理化学的分子間相互作用、生物工学的分子・細胞間相互作用を検出可能な実験系を構築する。これを用いて、生理・病理活性の鍵となる分子相互作用を同定し、意義を解明し、阻害による病態修飾を図る。具体的には、IgSF分子検索系の構築、腫瘍免疫、がん転移、ウイルス感染の鍵となる分子相互作用の同定と解析、多彩な細胞接着分子病の解明を行う。
|
| 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.
|
| 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。
|
Report
(3 results)
Research Products
(18 results)
-
-
-
[Journal Article] Trans-homophilic interaction of CADM1 promotes organ infiltration of T-cell lymphoma by adhesion to vascular endothelium.2022
Author(s)
Kasai Y, Gan SP, Funaki T, Ohashi-Kumagai Y, Tominaga M, Shiu S-J, Suzuki D, Matsubara D, Sakamoto T, Sakurai-Yageta M, Ito T, Murakami Y.
-
Journal Title
Cancer Science
Volume: in press
Issue: 5
Pages: 1-2
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Novel mechanisms of EGFR-TKI resistance and clonal evolution of lung adenocarcinoma by over expression of a cell adhesion molecule, CADM1.2020
Author(s)
Tsuchiya T, Kuwano H, Ito T, Nagata M, Kawai T, Matsubara D, Okamoto I, Tamura K, Nakajima J, Oba M, Murakami Y.
Organizer
AACR Special Conference, Tumor Heterogeneity
Related Report
Int'l Joint Research
-
-
