2022 Fiscal Year Final Research Report
Determination of liver metastasis preventive compounds targeting Amigo2 molecule for extrapolation to humans
| Project/Area Number |
20K07447
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 49030:Experimental pathology-related
|
|---|
| Research Institution | Tottori University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2020-04-01 – 2023-03-31
|
| Keywords | AMIGO2 / 肝転移 / ドライバー分子 / 外挿 |
|---|
| Outline of Final Research Achievements |
We determined the liver metastasis driver AMIGO2 from mouse fibrosarcoma cells and identified 10 compounds that suppress AMIGO2 expression. There were 5 targets common to these 10 compounds. 1) The function of AMIGO2 as a driver of liver metastasis can be extrapolated to human cancer cells. 2) We succeeded in drug repositioning with 3 types of clinical molecular targeted drugs that inhibit 5 types of signaling pathways. 3) Adhesion of human cancer cells to human hepatic vascular endothelium was inhibited by treatment with molecular targeted drugs. 4) Molecular targeted drugs inhibited liver metastasis in nude mice. Based on these findings, the liver metastasis driver AMIGO2 was a universal functional molecule across species. In this study, we obtained the target of drug repositioning and determined compound candidates. We are going to move on to analyze the detailed structure of the compound that suppresses liver metastasis.
|
| Free Research Field |
実験病理学
|
| Academic Significance and Societal Importance of the Research Achievements |
原発腫瘍の治療後に控える遠隔転移は，患者予後を決定する最大のリスク要因となる．特に肝転移は，生命維持の主機能が損なわれるだけで無く，脳・肺への二次転移に繋がる．従って，癌診断時より肝転移の予防化合物の投与が叶えば，癌患者の抱く潜在的な癌死への恐怖を払拭する希求の転移予防開発に応える意義を持つことになる．本研究成果は，肝転移予防化合物の開発，そして提供に繋がる波及効果を有する．
|
