癌リスクの多臓器マッピング
Liqin Zhu1, David Finkelstein2, Culian Gao3
1Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Cell
|August 28, 2016
まとめ
癌のリスクは,突然変異した幹細胞の 生殖能力によって決定されます. 損傷などの幹細胞の増殖を促す要因は 癌のリスクを大幅に高め 腫瘍の発生に"完璧な嵐"を生み出します
科学分野:
- 細胞生物学
- 癌の研究
- 臓器生成
背景:
- 癌の発生率は臓器によって異なりますが,幹細胞機能のような内在的な細胞因子の役割は,臓器特異的な癌リスクを決定する上で不明です.
- 細胞の内在的な性質が癌の感受性に与える影響を理解することは,標的型の予防と治療戦略を策定する上で極めて重要です.
研究 の 目的:
- 幹細胞と非幹細胞の腫瘍発生に対する生涯の感受性を調査する.
- 幹細胞の機能が臓器がんのリスクの 決定要因であるかどうかを判断する
主な方法:
- マウスモデルで条件付き系統追跡,腫瘍遺伝子,腫瘍抑制アレルのクレ再結合を用いた.
- 幹細胞と非幹細胞の集団を定義し,その生涯を通じて追跡する.
- 肝臓を含む様々な臓器系の変異細胞の腫瘍発生可能性を評価した.
主要な成果:
- 腫瘍の発生率は,遺伝子型や発達段階に関係なく,生涯にわたる変異細胞の生成能力と直接相関していた.
- 幹細胞は臓器がんのリスクの主な決定因子として特定されました.
- 肝臓モデルにおける幹細胞機能の損傷誘発による活性化により,癌のリスクが顕著に増加した.
結論:
- 幹細胞の機能は 臓器がんリスクを決定する 重要な内在的要因です
- 幹細胞変異と幹細胞増殖を促す外的要因の組み合わせにより,がんの発症の高リスクシナリオが生まれます.
- これらの発見は癌の発症と進行における 幹細胞の重要な役割を強調しています
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