| Project/Area Number |
20H03758
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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 55020:Digestive surgery-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2022: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2021: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2020: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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| Keywords | がん / 炎症 / 組織再生 |
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| Outline of Research at the Start |
がん死亡の約9割はがんの転移によると考えられているが、現在、がん転移の予防や治療に有効な方法がなく、新しい予防・治療方法の開発が強く望まれている。本研究では大腸がん細胞自身が引き起こす炎症どのようにがん微小環境に影響してがんの発生や浸潤・転移に寄与しているかのメカニズムを明らかにすることを目的とし、その知見を元にヒトに応用できる新しい大腸がん転移予防・治療法の開発を目指す。
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| Outline of Final Research Achievements |
It is known that chronic inflammation contributes to invasion and metastasis of many cancers, but the detailed mechanism is still unknown. To artificially control anti-tumor immunity, it is important to clarify the molecules and cell types that regulate chronic inflammation in the tumor microenvironment. In this study, we examined how driver gene mutations and inflammatory regenerative signals regulate production of cytokines, chemokines and growth factors produced by cancer cells and how these molecules affect chronic inflammation and anti-tumor immunity in the tumor microenvironment by using new technologies such as organoid culture, CRISPR/Cas9 system, and comprehensive analysis. For that purpose, we have established genetically modified organoids, which were mutated with oncogenes and tumor suppressor genes that are important in the multi-stage carcinogenesis hypothesis of colorectal cancer, and analyzed gene expression of these organoids.
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| Academic Significance and Societal Importance of the Research Achievements |
今回は新規技術である腸オルガノイド培養や網羅解析、CRISPR/Cas9によるゲノム編集などを用いて、がん細胞自身のドライバー遺伝子変異やそれに伴う炎症（新規炎症シグナル伝達経路Src-YAP経路やJAK-STAT3経路）がどのようにがん免疫に影響を与えるかという新しい観点から研究を行っており、新規がん治療方法の開発に繋がることが期待される。
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