| Project/Area Number |
17H04377
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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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| Research Field |
Pathobiological dentistry/Dental radiology
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
波多 賢二 大阪大学, 歯学研究科, 准教授 (80444496)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2017: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
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| Keywords | がん / 知覚神経 / 骨転移 / 骨 / プロトンポンプ / TRPV1 / 骨痛 / 神経 |
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| Outline of Final Research Achievements |
Majority of cancer patients suffer from cancer pain at advanced and terminal stage of the illness. However, the mechanism underlying cancer pain remains unclear and currently-available therapeutic means are not satisfactorily effective at reducing cancer pain, resulting in decreased survival of cancer patients. In this study, we found that the acidic microenvironment created by breast cancer is responsible for causing bone pain using an animal model of cancer pain. We then showed that a synthetic small compound and a natural substance that block the actions of the acidic microenvironment reduced bone pain, and the progression of breast cancer in bone and metastasis to lung from bone. These results suggest that bone pain and breast cancer progression are reciprocally interactive and that bone pain biologically regulates cancer progression and secondary metastasis from bone and support the notion that the acidic microenvironment associated with cancer is a potential therapeutic target.
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| Academic Significance and Societal Importance of the Research Achievements |
血管の新生はがんの増大に不可欠である。しかし、血管の新生と連動して起こる神経の新生とがんの増大との関係は不明である。本研究は、増大するがん周囲の酸性環境による骨内の知覚神経の興奮、すなわちがん性骨痛、により知覚神経でのがん増殖促進因子の産生が高まり、その結果骨内でのがんの増大、骨からの二次転移が強まることを分子細胞生物学的に明らかにした。本成果は、がん患者を最も苦しめ、その治療を困難にする要因の一つであるがん性骨痛を抑え込むことにより、同時にがん自体の進展に対しても一石二鳥的に抑制効果が得られることを示唆し、今後のがん治療にこれまでになかった視点からのアプローチをもたらすと期待される。
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