| Project/Area Number |
18K07196
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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 50010:Tumor biology-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 大腸癌 / 腫瘍微小環境 / 好中球 / 血管新生 / マウスモデル / .腫瘍微小環境 |
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| Outline of Final Research Achievements |
In this study, we tried to reveal tumor promotive function of neutrophils in the tumor microenvironment of colon cancer, using mouse models of colon cancer. Neutrophil is one of the important host immune cells. However, it is also known that neutrophils promote tumor progression in the tumor microenvironment. It becomes an attractive therapeutic strategy to suppress only tumor promotive function of the neutrophils without affecting protective function against infection. CMS4 colon cancer shows poor prognosis, with resistance to anti-VEGF treatment. We found that neutrophils accumulated in the tumor microenvironment of CMS4 mouse colon cancer, secreting Bv8 angiogenic factor. When treating anti-Bv8 antibody in addition to anti VEGF antibody, tumor formation of CMS4 mouse colon cancer was suppressed.
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| Academic Significance and Societal Importance of the Research Achievements |
CMS4大腸癌は予後不良で、大腸癌治療のキードラッグの抗VEGF治療に抵抗性を示すことが知られている。今回我々の研究では、CMS4大腸癌の抗VEGF治療耐性に好中球が深く関与すること、好中球由来の血管新生因子Bv8をVEGFとともに阻害することで、抗VEGF治療耐性が解除されることを、自然発生大腸癌マウスモデルを用いることで、より実臨床に近い環境で解明した。本邦において、大腸癌はがん死亡数では肺癌に次ぐ２番目の死亡数で、最新がん統計によると2019年は約5万人が大腸癌で死亡したとされる。本研究結果が臨床応用されれば、これらの患者の治療に有用である可能性がある。
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