| Project/Area Number |
18H02759
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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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| Review Section |
Basic Section 52040:Radiological sciences-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
及川 司 北海道大学, 医学研究院, 講師 (20457055)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2019: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Keywords | 放射線 / 代謝協調 / 細胞間相互作用 / 糖代謝 / 共培養 / 代謝 / 放射線耐性 / 治療耐性 |
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| Outline of Final Research Achievements |
Using cell-specific regulation of glucose metabolism, we co-cultured glucose-sufficient and glucose-deficient cancer cells and established "metabolic cooperation" between them to analyze viability, intracellular metabolism, phenotypic changes, and response to radiation. The above experimental system revealed that cancer cells in a glucose-depleted state maintain their viability by obtaining metabolites from glucose-sufficient cells, and that oxidative stress and ER stress in the former cells are markedly suppressed. Estimation of the mediating substances and mechanisms, as well as the various phenotypic changes that occur in the metabolic cooperative state, are currently under analysis.
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| Academic Significance and Societal Importance of the Research Achievements |
腫瘍の内部はがん細胞の盛んな増殖と代謝変化とが相まって、しばしば栄養素や酸素の欠乏領域を生じる。そのような領域では薬剤や放射線の効果、および免疫細胞の作用が抑制されるため、治療効率が低下する。また、申請者自身の解析により、栄養素欠乏領域の存在は、周囲のがん細胞も含めた腫瘍全体の治療耐性亢進を誘導することが明らかとなった。栄養欠乏領域のがん細胞は、周囲の細胞の中間代謝産物を利用して生存性を維持している。このような「代謝協調」のメカニズムを明らかにし、それに基づき飢餓領域において細胞死を効率よく誘導する方法を確立できれば、既存の治療法の効率をより高めることができると考えられる。
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