治療後半年以内に致死的な再発を引き起こす膠芽腫において、グリオーマ幹細胞（Glioma stem cell, GSC）は周囲環境への依存性が低く、生存、増殖に有利な成分を分泌することで自らニッチを形成する。しかし、そのような自律性ニッチの特性は十分に解明されていない。本研究では自律性ニッチの成立過程の可視化に成功し、そのニッチが腫瘍塊の周辺のみならず、離れた正常脳にも形成されることを明らかにした。また、低分子阻害剤スクリーニングより自律性ニッチの破綻を誘導する薬剤を複数同定した。
Glioblastomas are fatal because they recur within months after treatment, with limited options for additional therapy. Glioma stem cells (GSCs), the cells causing recurrence form their own niche by secreting components favorable for survival and proliferation. However, the characteristics of the GSC autonomous niche have not been fully elucidated. In this study, we recorded the formation process of the autonomous niche and showed that, consistent with the recurrence patterns of glioblastomas, the niche is formed not only around the tumor mass but also in distant areas within the normal brain. Furthermore, through screening of small molecule inhibitors, we identified several drugs that disrupt the autonomic niche.Importantly, systemic factors were found to significantly influence the response of the tumor to these inhibitors. Further investigations of the interaction of the autonomous niche with systemic factors will thus be necessary to establish anti-niche therapies.

研究種目 : 基盤研究 (C) (一般)
研究期間 : 2019～2021
課題番号 : 19K07671
研究分野 : 腫瘍生物学