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「放射線抵抗性浸潤細胞」への変換に関わる機序の解明と抑制方法の提案

阐明向“放射抗性浸润细胞”转化的机制并提出抑制方法

基本信息

批准号：
22K07786
负责人：
藤田真由美
金额：
$ 2.66万
依托单位：
National Institutes for Quantum Science and Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2022
资助国家：
日本
起止时间：
2022-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22K07786/
关键词：
浸潤放射線放射線抵抗性浸潤細胞転移放射線治療

项目摘要

我々はこれまでの研究にて、ある特定の細胞株では、細胞全体の中に一部「放射線抵抗性浸潤細胞」が存在することを明らかにしてきた。また「放射線抵抗性浸潤細胞」の特徴から、放射線に対する抵抗性や、浸潤・転移を抑制することにも成功している。しかし「放射線抵抗性浸潤細胞」の特徴につながるパスウェイはいくつもあるため、その全てを阻害するためには複数の阻害剤を使用する必要があり、臨床への応用を考えると現実的な抑制方法ではなかった。そこで本課題では発想を転換し、そもそも「放射線抵抗性浸潤細胞」はどのように出現するのか、メカニズムを解明することを計画した。遺伝的なバックグラウンドが同じ細胞株の中で、一部の細胞でのみ「放射線抵抗性浸潤細胞」が出現することから、エピゲノムの変化が関与するであろうことが予想できた。またメタボローム解析を用いた研究にて、「放射線抵抗性浸潤細胞」は全体の細胞集団と比較し、代謝産物の蓄積が顕著に異なることをすでに見出しており、中でもTCAサイクルの中間代謝産物の産生量の差についての意義は不明であった。TCAサイクルの中間代謝産物は、近年エピゲノムを変化させる上流因子として着目されている。そこで本研究では、TCAサイクルの中間代謝産物に焦点をあて、「放射線抵抗性浸潤細胞」への性質転換における意義を調べることとした。具体的には、まず①浸潤能力や放射線抵抗性の獲得を促すTCA中間代謝産物を特定する、次に②特定されたTCA中間代謝産物による性質転換（浸潤能力や放射線抵抗性の獲得）に、エピゲノムの変化が関与していたか明らかにする。さらに、③細胞の性質転換（浸潤能力や放射線抵抗性の獲得）でキーとなるTCA中間代謝産物の蓄積は、実際にこれまで見出してきた「放射線抵抗性浸潤細胞」で確認されるか明らかにする、ことを計画し、2022年度 (初年度) は①を中心に遂行した。

In our research program, there is a "radiation-line resistance immersion cell" in the study of specific cell lines and the whole cell population. Radiation-resistant cells were immersed in radiation-resistant cells, radiation-resistant cells and radiation-resistant cells. In this paper, we use the method of radiation resistance, radiation resistance. In this project, you want to make sure that you have a problem with radiation resistance, and that you have a problem with radiation resistance. This is the same as that of the cell line in which the radiation resistance of the cell line is the same as that of the cell line, which is the same as that of the cell line. In this paper, we use the methods of research, radiation resistance immersion, whole cell collection, data storage and data acquisition. The data of the whole cell collection were compared, and the data of the whole cell collection were analyzed. The data of the whole cell collection were compared, and the data of the whole cell collection were analyzed. The data of the whole cell set were collected and analyzed. The data of the whole cell collection were collected and analyzed. The data of the whole cell collection were collected and analyzed. The data of the whole cell collection were collected and analyzed. The data of the whole cell collection were collected and analyzed. The data of the whole cell collection were collected. The meaning of the product was not clear. In the TCA test, there was an unknown meaning. In recent years, TCA has been focusing on the upstream factors in recent years. In this study, TCA was used to determine the focus of radiation resistance, and the meaning of "radiation resistance immersion cell". The specific immersion ability, radiation line resistance, radiation line resistance, and so on, in the TCA, in the second and second specific TCA, the specific immersion ability, the radiation line resistance, the specific immersion ability, the radiation line resistance, the radiation line resistance, the specific immersion ability, the radiation line resistance, the radiation line resistance, the specific immersion ability, the radiation line resistance, the radiation line resistance, the specific immersion ability, the specific immersion ability, the radiation line resistance, the radiation line resistance, the specific immersion ability, the radiation line resistance, the radiation line resistance, the specific immersion ability, the radiation line resistance, the radiation line resistance, the specific immersion ability, the specific immersion ability, the radiation line resistance, the specific immersion ability, the radiation line resistance, the radiation line resistance, the radiation line resistance In this paper, the results show that there is a significant increase in the number of products in the TCA. In this paper, the results show that there is a significant increase in the number of products in the TCA. In this paper, the results show that there is a significant increase in the level of radiation resistance in the first year of the year.