The physiological roles of proton-sensing GPCRs in tumor-associated macrophages
| Project/Area Number |
17K15457
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pharmacology in pharmacy
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 腫瘍 / プロトン感知性受容体 / 腫瘍関連マクロファージ / Gタンパク質共役型受容体 / 癌 / マクロファージ |
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| Outline of Final Research Achievements |
In solid tumors pH reduction is observed, however, the physiological importance of pH reduction in the surrounding normal cells and immune cells other than tumor cells remains largely unknown. Therefore, in this study, we focused on elucidating the physiological mechanism of pH reduction in tumor-associated macrophages (TAM). As a result, we found that TDAG8, which is one of proton-sensing GPCRs that are activated in acidic conditions, is highly expressed in TAM in colon cancer model mice and tumor cell subcutaneously inoculated model mice. In addition, we generated macrophage-specific TDAG8 deficient mice.
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| Academic Significance and Societal Importance of the Research Achievements |
腫瘍関連マクロファージ（TAM）の腫瘍組織内への浸潤増加は、悪性度および予後の悪化と正の相関関係を示すことから、治療標的細胞として注目されている。本研究よってTDAG8がTAMに高発現していることを見出し、TDAG8は炎症に関与するとの従来の報告を合わせると、TDAG8が腫瘍形成に関与する可能性が高いことが考えられ、TDAG8が新たな腫瘍の治療標的としての可能性が期待される。加えて、本研究にて作製したマクロファージ特異的なTDAG8欠損マウスは、腫瘍形成のみならず、マクロファージが関与するとされる様々な疾患におけるTDAG8の生理的役割の解明にも応用可能と考えている。
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Report
(3 results)
Research Products
(8 results)
