EMT中に発生する腫瘍の移行状態の特定
Ievgenia Pastushenko1, Audrey Brisebarre1, Alejandro Sifrim2,3
1Laboratory of Stem Cells and Cancer, Université Libre de Buxelles, Brussels, Belgium.
Nature
|April 20, 2018
まとめ
癌における上皮からメゼンキマへの移行 (EMT) は,バイナリー状態だけでなく,中間状態を含みます. 研究者は,これらのEMT段階をインビボで反映した異なる腫瘍サブ集団を特定し,可塑性および転移の違いを明らかにしました.
科学分野:
- 腫瘍学
- 細胞生物学
- 癌 研究
背景:
- エピテリアからメゼンキマへの移行 (EMT) は,腫瘍幹,転移,および治療耐性に関連して,がんにおいて極めて重要です.
- EMTはシンプルなバイナリースイッチではなく 状態のスペクトルとして見られています
- 腫瘍における明瞭な中間EMT状態の直接のインビボ証拠は欠けています.
研究 の 目的:
- 主要な腫瘍における間層からメゼンキマへの移行状態 (EMT) の存在と特徴を in vivo で調査する.
- 異なるEMT段階に関連した異なる腫瘍サブ集団を特定し,特徴づけること.
- EMTの移行に関する規制メカニズムとニッチの影響を探求する.
主な方法:
- 細胞表面マーカーの大きなパネルのスクリーニング
- 特定された腫瘍サブ集団の転写と表遺伝的景観の分析.
- 腫瘍の増殖能力,細胞の可塑性,侵入性,転移の可能性の評価
- 異なるニッチ内の腫瘍サブ集団の局所化研究.
主要な成果:
- エピテリア,メゼンキマ,および中間ハイブリッドEMT状態を表す複数の腫瘍サブ集団のインビヴォの特定.
- すべてのEMTサブポピュレーションは,同様の腫瘍増殖能力を示した.
- 細胞の可塑性,侵入性,転移の可能性の差異が観察されました.
- EMT状態を制御する遺伝子規制ネットワーク,転写因子,シグナル伝達経路が解明されました.
- EMTを差異的に調節する異なるニッチで腫瘍のサブ集団が見つかりました.
結論:
- 癌におけるEMTは,インビボの証拠によって支持される中間の状態の連続を通して発生します.
- 異なるEMTサブポピュレーションは,異なった転移の可能性と細胞の可塑性を持っています.
- ニッチマイクロ環境は,腫瘍内のEMTダイナミクスを調節する上で重要な役割を果たします.
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