| Project/Area Number |
18K08571
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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 55010:General surgery and pediatric surgery-related
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| Research Institution | Okayama University |
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Principal Investigator |
Yoshimura Teizo 岡山大学, 医歯薬学総合研究科, 非常勤研究員 (50174991)
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| Co-Investigator(Kenkyū-buntansha) |
松川 昭博 岡山大学, 医歯薬学総合研究科, 教授 (90264283)
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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 |
¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Keywords | がん微小環境 / ケモカイン / 乳癌 / マウスモデル / マクロファージ / 線維芽細胞 / 白血球遊走因子 / 乳がん / 白血球遊走因子レセプター / 好中球 / 血管新生 / 白血球 / 遊走因子レセプター / Formylpeptideレセプター / がん転移 / Breast cancer / Chemoattractant / Chemoattractant receptor / Tumor microenvironment / Leukocytes |
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| Outline of Final Research Achievements |
Tumor infiltrating leukocytes play an important role in the progression of cancer. In this study, we examined the role of the classical chemoattractant receptor Fpr expressed by non-tumor cells in the progression of breast cancer using a transplantable 4T1 mouse breast cancer model. Tumors grew at a similar rate in both strains at the injected sites; however, lung metastases were significantly reduced in Fpr2-deficient mice independently of the chemokine MCP-1 because serum MCP-1 levels were similar between tumor-bearing WT and Fpr2-deficient mice. In tumors of Fpr2-deficient mice, the development of blood vessels was weaker and necrosis of tumor tissue was more apparent. Ly6G+ neutrophils were detected mainly in the peripheral area and did not infiltrate inside tumors. Thus, Fpr2+ neutrophils appear to play a role in the progression of 4T1 breast cancer. Studies focusing on Fprs may lead to the identification of new targets and a potential prevention of breast cancer metastasis.
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| Academic Significance and Societal Importance of the Research Achievements |
腫瘍組織内への免疫抑制性好中球やマクロファージの浸潤、それに伴う腫瘍進展への影響に関しては主にケモカインやそのレセプターを焦点とした多くの研究が行われている。しかし、Fprなどの古典的な白血球遊走因子レセプターの役割に関しての情報は限られている。本研究では、Fprの一つであるFpr2欠損マウスを使いFpr2の作用により浸潤した白血球が4T1乳癌の肺転移を促進していることを強く示唆する結果を見出し、このレセプターが今後乳癌の肺転移予防のためのターゲットになる可能性が示唆された。本研究の結果はFprの阻害が乳癌の肺転移を予防できる可能性を示すもので社会的意義が大きいと思われる。
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