| Project/Area Number |
18K09311
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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 56050:Otorhinolaryngology-related
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| Research Institution | Akita University |
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Principal Investigator |
Kawasaki Yohei 秋田大学, 医学部附属病院, 講師 (00644072)
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| Project Period (FY) |
2018-04-01 – 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 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | LAT1 / CD98 / 放射線抵抗性 / 頭頸部扁平上皮癌 / LAT-1 / CD98hc / 癌幹細胞 / CD44v9 / 放射線耐性 |
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| Outline of Final Research Achievements |
CD98 is a membrane protein composed of heavy and light chains. Overexpression of CD98 heavy chain has been found to be a poor prognostic factor in a variety of cancers. We reported that CD98 heavy chain is a marker of cancer stem cells in head and neck of squamous cell carcinoma. On the other hand, CD98 light chain is an amino acid transporter, and it is beginning to be elucidated that LAT1 is specifically expressed in cancer cells. Its function is not clear in head and neck of squamous cell carcinoma. We have shown that LAT1-positive cells are involved in malignancy and contribute to therapeutic resistance. And the present study suggests that inhibiting CD98 light chains may be able to kill cancer stem cells. We will investigate the association with CD44v9, a cancer stem cell marker.
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| Academic Significance and Societal Importance of the Research Achievements |
頭頸部扁平上皮癌のCD98軽鎖であるLAT1は悪性度に関与し、臨床検体からもLAT1の発現が高い群は予後不良であることが明らかとなった。特に、放射線化学療法に対しては顕著に抵抗性があることがわかった。LAT1の阻害薬JPH203によって、頭頸部扁平上皮癌の通常株や放射線耐性株の働きが大きく抑えられた事は大きな発見である。今後、LAT1の発現が高い頭頸部扁平上皮癌や再発症例に対して、LAT1を阻害するという治療の開発につながると思われる。元々予後不良である頭頸部扁平上皮癌の予後改善を目指せる新規治療法につながるとして、大きな学術的、社会的意義がある。
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