| Project/Area Number |
17K16483
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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 |
Radiation science
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| Research Institution | Keio University |
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Principal Investigator |
KOTA Ryuichi 慶應義塾大学, 医学部(信濃町), 助教 (00464834)
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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 |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 放射線抵抗性 / セネッセンス / グリオーマ幹細胞 / グリオーマ |
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| Outline of Final Research Achievements |
The purpose of this study is to elucidate the acquired radiation resistance of brain tumor cells, which is enhanced by irradiation itself. In this study, murine glioma stem cells (iGSC) were used as model cells of human giloblastoma stem cells.As a result of the analysis, it was revealed that a single dose of 10Gy irradiation caused cellular senescence, and the expression of a secretory protein IGFBP3 was decreased.
In general, it is known that the IGF signal is fortified in an environment with a low amount of IGFBP3. Also in iGSC, it was confirmed that the expression of phosphorylated Akt was increased downstream of IGF. These findings suggest that cellular survival signals are activated by a radiation-induced low IGFBP3 extracellular environment.
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| Academic Significance and Societal Importance of the Research Achievements |
グリオブラストーマは極めて悪性度の高い治癒困難な悪性脳腫瘍である。放射線治療の処方線量を増やすようなシンプルな手法では治療成績改善につながらないことが分かっている。そのため放射線治療抵抗性の要因を解除するようなアプローチが治療成績改善のために必要となる。本研究ではグリオーマ幹細胞に対する放射線照射により細胞老化が誘導され、分泌タンパクの一種であるIGFBP3の低下が生存しているグリオーマ幹細胞の放射線抵抗性に寄与していることが示された。これは新たな知見であり、今後悪性脳腫瘍に対する放射線治療の線量分割法を考慮する上で基礎的なバックボーンを与える知見となり得る。
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