Identification and functional analysis of a liver stromal cell-derived factor contributing to liver metastasis of colorectal cancer cells
| Project/Area Number |
18K08693
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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 55020:Digestive surgery-related
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| Research Institution | Microbial Chemistry Research Foundation |
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Principal Investigator |
Tomokazu Ohishi 公益財団法人微生物化学研究会, 微生物化学研究所 沼津支所, 主任研究員 (50442546)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | がんー間質相互作用 / がん-間質相互作用 / 大腸がん / がん－間質相互作用 / 大腸がん肝転移 / がん関連線維芽細胞 |
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| Outline of Final Research Achievements |
In this study, we tried to identify a novel molecule, which is involved in the liver metastasis of colorectal cancer. We sought the possibility of a new therapeutic strategy targeting the molecule for the treatment of liver metastasis of colorectal cancer. 1)Plasminogen activator inhibitor-1 (PAI-1), a negative regulator of the fibrinolytic pathway is identified as a candidate of promoting factor of liver metastasis of colorectal cancer. 2) Treatment of PAI-1 inhibitor suppressed liver metastasis of colorectal cancer in a mouse model of liver metastasis of colorectal cancer. 3)Similarly, PAI-1 knockout mice suppressed liver metastasis of colorectal cancer compared with wild-type mice.
Taken together, PAI-1 promotes liver metastasis of colorectal cancer and inhibition of PAI-1 may suppress liver metastasis of colorectal cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
大腸がんは国内罹患数が最も高いがんであり、早急な対応が急務である。大腸がんの転移は患者の予後不良に直結し、約7~8割を占める大腸がん肝転移の制御が重要である。現在、抗上皮成長因子受容体（EGFR）抗体薬が推奨されていないRAS変異型の大腸がん患者の存在が問題となっており、新たな治療戦略が求められてきた。我々が見出したPAI-1は大腸がん肝転移を促進する因子であることから、新たな治療標的として考えられる。その阻害剤や中和抗体は、抗EGFR抗体薬不応性のがんにも適用できると見込まれ、社会的意義は大きい。
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Report
(4 results)
Research Products
(17 results)
