2020 Fiscal Year Final Research Report
Hypoxia-responsive CD73 promotes the growth and migration of pleomorphic adenoma cells
| Project/Area Number |
18K09740
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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 57060:Surgical dentistry-related
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| Research Institution | Niigata University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山崎 学 新潟大学, 医歯学系, 助教 (10547516)
田沼 順一 新潟大学, 医歯学系, 教授 (20305139)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | hypoxia / HIF-1α / CD73 / pleomorphic adenoma |
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| Outline of Final Research Achievements |
In this study, we investigated the role of CD73, one of the target molecules of the hypoxia inducible factors (HIF) activation mechanism, in cell function under hypoxia. We cultured SM-AP cells, which were established from a human pleomorphic adenoma, under normal or hypoxic conditions, and examined the expression of HIF-1α and CD73, as well as cell migration and proliferation when the level of CD73 synthesis was controlled by siRNA. The HIF-1α gene and protein were highly expressed in the nucleus under hypoxic conditions for 48 hours, and CD73 expression was also highly expressed. Under hypoxic conditions, the cell migration ability was enhanced compared to normal culture conditions. On the other hand, when CD73 expression was suppressed, cell proliferation was inhibited. These results suggest that activation of HIF-1α under hypoxic conditions promotes cell proliferation and migration of pleomorphic adenoma cells through their own high expression of CD73.
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| Free Research Field |
口腔病理学
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| Academic Significance and Societal Importance of the Research Achievements |
腫瘍は低酸素状態(Hypoxia)という特異な微小環境下において、低酸素誘導因子(Hypoxia inducible factors: HIF)により引き起こされる低酸素応答を介した生存・増殖をおこなっている。今回、我々はHIF活性化機構の標的分子の一つであるCD73が低酸素下で細胞機能に果たす役割を検討した。その結果、低酸素状態でHIF-1αを活性化させることで、多形腺腫細胞は自身がCD73を高発現させ、細胞の増殖・遊走を促進していることが示唆された。CD73を介した腫瘍細胞自身の腫瘍特異的な低酸素応答性増殖機構を標的とした新たな抗腫瘍治療への展望を見出すことができたと考える。
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