| Project/Area Number |
20K18314
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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 56050:Otorhinolaryngology-related
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| Research Institution | Ehime University |
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Principal Investigator |
Kitani Takashi 愛媛大学, 医学部附属病院, 助教 (00568909)
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 頭頸部扁平上皮癌 / リンパ節転移 / NHE1 / LOXL2 / 転移抑制治療 / HNSCC / 頭頚部癌 / collective migration |
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| Outline of Research at the Start |
頭頚部扁平上皮癌の予後はリンパ節転移の有無により大きく左右される。申請者らはこれまでにナトリウムイオン／プロトン交換輸送体（NHE1）が頭頚部癌のリンパ節転移に関連することを見出し、NHE1が新規の治療標的に値する分子となり得ると考えられた。本研究ではNHE1発現を阻害することで頭頚部扁平上皮癌のリンパ節転移抑制を試み、また臨床検体からNHE1の予後因子としての有用性を検討する。
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| Outline of Final Research Achievements |
The full picture of the phenomenon of cancer metastasis is still unclear. Although many factors have been reported to contribute to cancer metastasis, therapies targeting metastasis itself have not yet been developed for practical use. In this study, we aimed to inhibit metastasis of head and neck squamous cell carcinoma(HNSCC) more efficiently by simultaneously inhibiting two factors, Na+/H+ exchanger-1(NHE1) and lysyl oxidase-like- 2(LOXL2), which were found to be involved in HNSCC metastasis in previous studies. In mice transplanted with a human tongue squamous cell carcinoma cell line, a statistically significant reduction in metastasis rate was observed in the group in which these two factors were simultaneously suppressed compared to the negative control group. The simultaneous suppression of these two factors, which have different mechanisms, is expected to suppress metastasis to a higher degree.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、NHE1を治療標的とすることでいまだ実用化の例のない「転移抑制治療」開発に挑む大きな研究の一部をなしている。転移抑制治療は従来の腫瘍細胞を殺傷することを目指す癌治療とは治療戦略が異なる。したがって両者を組み合わせることで、より効果的な相加的効果あるいは相乗的効果を持つ新規がん治療の創出を企図しているという点において、高い社会的意義を持っている。
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