Elucidation of cancer stem cell niche components and signaling by bioactive polymer arrays

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02678
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: TAGA Tetsuya 東京医科歯科大学, 難治疾患研究所, 教授 (40192629)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 生物機能性ポリマー / 癌幹細胞 / ニッチ / 脳腫瘍 / 神経膠芽腫 / 鉄代謝 / オートスキジス

Outline of Final Research Achievements

This study has demonstrated the usefulness of synthetic polymer scaffolds as a tool for comprehensively elucidating glioma stem cell niche, by revealing iron that regulates glioma stem cell maintenance and glioma expansion. This finding provides a new self-expanding strategy of glioma stem cells that systemically exploits erythroid lineages to reconstruct GSC-friendly niche. In this study, it is also revealed that glioma stem cell-derived necrotic particles designated as autoschizis-like products play a key role in developing a glioma stem cell-supportive subset of tumor-associated macrophages. This finding thus demonstrates that glioma necrosis is not a meaningless death but is a tumor-beneficial event. Taken together, a series of these studies will provide new insights into the mechanisms underlying glioma stem cell-driven niche development as well as glioma progression and recurrence.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

癌幹細胞は治療抵抗性を有し癌の進展や転移に寄与するため癌根絶において重要な治療標的として認識される。その微小環境である癌幹細胞ニッチの解明は癌幹細胞性の消失に向かわせる手掛かりになるが、癌幹細胞ニッチの構成要素は極めて多岐に渡るため全容解明は困難であった。本研究において、癌幹細胞を維持する働きをもつ生物機能性ポリマーを用いて鉄代謝という癌幹細胞ニッチ要素を同定したことを端緒にして癌幹細胞が生体の赤血球分化を利己的に制御してニッチを構築することおよび、癌幹細胞が特殊な細胞死を介して生体の免疫細胞に作用して利己的なニッチ構築を行うことを示した。これら2つの新規概念は学術的にも社会的にも意義深い。