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Molecular mechanism underlying synapse development between neurons and glioma cells

神经元与胶质瘤细胞突触发育的分子机制

基本信息

批准号：
22K06429
负责人：
守村直子
金额：
$ 2.66万
依托单位：
Shiga University of Medical Science
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-22K06429/
关键词：
シナプス接着分子グリオーマシナプス形成

项目摘要

グリオーマは、進行が早く治療抵抗性の高い予後不良な悪性脳腫瘍である。近年、神経細胞とグリオーマ間で行われるシナプス伝達がグリオーマの悪性化を増強することがわかってきた。しかし、神経細胞とグリオーマ間を繋ぐシナプス接着分子や悪性化を誘導する分子群の役割につていは未だ不明な点が多い。本研究は、神経細胞間のシナプス形成やシナプス伝達を制御することが知られているポストシナプス接着分子LRFNファミリーを中心に、神経細胞とグリオーマ間のシナプス分子機序の詳細を明らかにして、神経細胞とグリオーマ間のシナプス伝達を断ち切る分子標的を発見すことが目的となっている。初年度の今年は、患者由来グリオーマ幹細胞（グリオブラストーマGBM）株の培養系を導入し、この細胞からRNAを抽出してRT-PCRによるLRFNの全長cDNAをクローニングを行なった。LRFNのmRNAの発現量は、未分化GBMで低く、分化したGBMで高いことがわかった。またクローニングによって同定されたものの中には、数種類の変異体が含まれていた。興味深いことに、膜貫通ドメイン上流で終始コドンを生じるものも含まれており、腫瘍悪性化には正常な膜貫通型と分泌型変異体の二面的な作用が想定された。さらに、クローニングしたcDNAをもとに、各種発現ベクターを構築し、タンパク質レベルの機能解析につなげるための実験ツールを整えることができた。ノックイン・ノックアウトなどのゲノム編集ツールの選定と作製、神経細胞ーグリオーマ細胞の共培養評価系確立、ウイルスベクターツール作製など、今後の研究推進に必要となる基本材料を調整することができた。

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