癌のグリコカリクスは,インテグリン媒介の成長と生存を機械的に優先する
Matthew J Paszek1, Christopher C DuFort2, Olivier Rossier3
11] Department of Surgery and Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, California 94143, USA [2] Bay Area Physical Sciences-Oncology Program, University of California, Berkeley, California 94720, USA [3] School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York 14853, USA [4] Laboratory for Atomic and Solid State Physics and Kavli Institute at Cornell for Nanoscale Science, Cornell University, Ithaca, New York 14853, USA.
Nature
|July 18, 2014
まとめ
悪性腫瘍の特徴は,大型グリコタンパク質に富んだ大型のグリコカリックスである. この構造は細胞粘着とシグナル伝達を強化し,進行がんの転移を促す可能性があります.
科学分野:
- バイオケミストリー バイオケミストリー
- 細胞生物学 細胞生物学
- がん研究 がん研究
背景:
- 悪性病は,細胞表面のグリカンとグリコタンパク質の変化と関連しています.
- 転移性腫瘍では,大量のグリコタンパク質の発現が増加し,細胞のグリコカリックスに影響を及ぼします.
研究 の 目的:
- 大容量のグリコカリックスが,インテグリン結合とシグナル伝達を強化することによって,腫瘍のフェノタイプを促進するかどうかを調査する.
- 超膜受容体の組織と機能における大型グリコプロテインの役割を決定する.
主な方法:
- 転移性腫瘍における上昇調節されたグリコプロテインを識別するためのグリコプロテイン発現シグネチャーを開発した.
- 感受体の機能に対するグリコプロテインの影響を予測するために,計算モデルを使用した.
- ヒト細胞におけるインテグリン粘着,クラスタリング,シグナル伝達に対するボリュックなグリコカリクスの効果を実験的にテストした.
- 進行した疾患患者の循環腫瘍細胞におけるグリコプロテイン発現を分析した.
主要な成果:
- Bulky glycocalyxは,アクトミオシン収縮性とは無関係な緊張を適用することによって,インテグリン集積を促進し,インテグリン状態を変更します.
- 変形していない細胞における腫瘍関連の大型グリコプロテインの発現は,焦点粘着アセンブリとインテグリン依存シグナル伝達を促進した.
- 大量のグリコタンパク質は,進行した疾患で循環する腫瘍細胞に豊富に存在します.
結論:
- 大容量のグリコカリクスは,転移を促進する腫瘍細胞の特徴です.
- 機械的に細胞表面受容体の機能を増強する大容量のグリコカリクスを介して,腫瘍細胞の成長,生存,転移を促す可能性があります.
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