2021 Fiscal Year Final Research Report
Development of a treatment for ALT-positive refractory tumors using iPS cells model of neuroblastoma tumorigenesis
| Project/Area Number |
19K16759
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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 50010:Tumor biology-related
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| Research Institution | Research Institute for Clinical Oncology Saitama Cancer Center |
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Principal Investigator |
Kyosuke Mukae 地方独立行政法人埼玉県立病院機構埼玉県立がんセンター(臨床腫瘍研究所), 臨床腫瘍研究所, 研究員 (60793974)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | iPS / 神経堤細胞 / ATRX / ALT / APB |
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| Outline of Final Research Achievements |
Li-Fraumeni syndrome iPSC-derived neural crest cells were cultured in soft agar medium to generate an ATRX-deficient lines, followed by clones that acquired scaffold-independent transformation. Furthermore, clones showing C-circle positive and APB formation were obtained. Using these clones, we attempted tumorigenesis by transplantation into subcutaneous and periadrenal adipose tissue of immune-deficient mice. Consistent with previous findings, TP53 mutant/ATRK-deficient cells were shown to be prone to acquire C-circle positivity. How these cells become cancerous is a future question.
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| Free Research Field |
がん
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、ATRX と ALT 経路の関係性に着目し、Li-F 症候群悪性形質転換 cNCC を利用して神経堤細胞におけるテロメア機構の一端を明らかにした。また、本研究のアプローチの意義は、iPS細胞を分化させ、発がんさせることにある。この方法が確立されれば、神経芽腫モデルに関わらず、その他のがんにも用いることができ、様々ながんにおける発生機構を追求することができるようになる。
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