腫瘍ストロマ内のメゼンキマ幹細胞は,乳がんの転移を促進する
Antoine E Karnoub1, Ajeeta B Dash, Annie P Vo
1Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Nature
|October 5, 2007
まとめ
メゼンキマ幹細胞は,乳がんの転移を促進する. 癌細胞は,これらの幹細胞をCCL5を分泌するように誘導し,癌細胞の運動性と拡散を促進し,CCL5/CCR5シグナル伝達に依存する可逆的なプロセスです.
科学分野:
- 腫瘍学 腫瘍学
- 幹細胞生物学 幹細胞生物学
- 癌の転移に関する研究
背景:
- メゼンキマ幹細胞 (MSC) は,乳腺腫瘍に存在します.
- 腫瘍の病理生理学におけるその役割は不明である.
研究 の 目的:
- 乳がんの病理生理学におけるMSCの関与を調査する.
- MSCが腫瘍転移に影響を与えるメカニズムを解明する.
主な方法:
- ヒトの骨髄由来MSCと,弱転移性ヒト乳がん細胞の併用注射.
- 皮膚下部部位における腫瘍異種移植の形成.
- ケモカイン分泌 (CCL5/RANTES) と受容体シグナル伝達 (CCR5) の分析.
主要な成果:
- MSCは,乳がん細胞の転移の可能性を大幅に増加させた.
- 乳がん細胞はMSCを刺激し,CCL5.5を分泌する.
- CCL5は,CCR5のシグナル伝達を通じて,がん細胞の運動性,侵入,転移を高めるために,パラクリン作用で作用した.
- 増幅された転移能力は可逆的であった.
結論:
- 腫瘍の微環境,特にMSCは,乳がん細胞の転移を可逆的に強化することができます.
- MSCによって分泌されるCCL5は,がん細胞の運動性と侵入を促進する上で重要な役割を果たします.
- MSC-CCL5-CCR5軸をターゲットにすることで,乳がんの転移を抑制する治療戦略を提供することができる.
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