協力するサブクローンによって維持される腫瘍細胞の異質性は,Wnt主導の乳がんにおいて維持される
Allison S Cleary1, Travis L Leonard1, Shelley A Gestl1
11] Jake Gittlen Laboratories for Cancer Research, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA [2] Penn State Hershey Cancer Institute, Pennsylvania State University College of Medicine, Hershey, Hershey, Pennsylvania 17033, USA.
Nature
|April 4, 2014
まとめ
乳がん細胞は,競合するだけでなく,協力することができる. この研究は,マウスの異なる腫瘍細胞サブクローンが成長のために互いに必要であることを示し,がん治療に対する新しい洞察を提供している.
科学分野:
- 腫瘍学 腫瘍学
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- 乳がんは,遺伝的に異なるサブクローンによって特徴付けられます.
- 腫瘍創生は細胞-細胞の協力の崩壊を伴うもので,サブクローンの競争につながります.
- 哺乳類の上皮腫瘍細胞サブクローンの間の機能的な協力に関する証拠は限られている.
研究 の 目的:
- ネズミの乳がんモデルにおけるクローン間協力の調査.
- 異なる腫瘍細胞サブクローンが腫瘍の維持に不可欠であるかどうかを判断する.
- Wnt経路の阻害下で腫瘍の回帰と再発のメカニズムを探求する.
主な方法:
- Wnt1過剰発現の乳がんのマウスモデルを使用した.
- 塩基底と光のサブクローンを区別するために,クローンマーカーとして体内のHras変異を採用した.
- 腫瘍の回帰と再発のダイナミクスを分析するために,Wnt離脱によるシミュレートされた標的療法.
主要な成果:
- いくつかのWnt駆動の乳腺腫瘍がバイクローナルであり,基礎のHras変異体と光のHras野生型のサブクローンを含むことを実証しました.
- 両方のサブクローンが腫瘍の増殖に必要であり,光で生成されたWnt1.1に依存していることが示されました.
- 基礎サブクローンは,Wnt離脱時にWnt生成細胞を募集することができ,サブクローンは,再発のためのWnt信号を再活性化するために進化することができます.
結論:
- 細胞間協力は,特定の乳がんの維持に不可欠である.
- 腫瘍細胞のサブクローンは,生存と成長のための協力的または競争的戦略を示すことができます.
- これらの協力的ダイナミクスを理解することで,ヒトのがんに対する新たな治療戦略を策定することができる.
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