| Project/Area Number |
18K16256
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | The University of Tokushima |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 腫瘍微小環境 / 糖代謝 / 癌間質線維芽細胞 / glucose / lactate / 腫瘍関連マクロファージ / 癌 / CAF / TAM / 代謝 |
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| Outline of Final Research Achievements |
Cancer‐associated fibroblasts (CAF) interact with cancer cells and play an important role in cancer initiation, growth, and metastasis. Furthermore Tumor associated macrophages(TAM) lead to cancer progression. This time, we focused on the metabolism in the tumor microenvironments. Cancer cells were cocultured with CAF or treated with CAF conditioned medium, after which their migration and invasion ability, epithelial‐mesenchymal transition (EMT)‐related marker expression and C‐X‐C motif chemokine 10 expression and secretion were detected. Lactic acid was significantly elevated in CAF. Furthermore, Macrophage Nrf2 activation by cancer cell-derived lactate skews macrophages polarization towards an M2-like phenotype and educated macrophages activate Nrf2 of the cancer cells to promote EMT of cancer cells. This study provides a new understanding of the role of Nrf2 in the cancer cell and TAM with lactate and VEGF signaling interaction and suggests a potential therapeutic target.
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| Academic Significance and Societal Importance of the Research Achievements |
化学療法、免疫療法の変化に遅れることなく、腫瘍関連線維芽細胞（CAF）/腫瘍関連マクロファージ（TAM）を中心とした腫瘍微小環境を介した抗腫瘍免疫のメカニズム解明、新規治療法に関する研究を行っていく必要がある。CAF制御により、治療抵抗性の問題を克服し、そのメカニズムを解明しようとする試みは、対象となる疾患すべてに応用できる可能性がある。
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