RANKLによる癌細胞移動と骨転移の調節
D Holstead Jones1, Tomoki Nakashima, Otto H Sanchez
1IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 3, A-1030 Vienna, Austria.
Nature
|March 31, 2006
まとめ
サイトカインRANKL (NF-kappaBリガンドの受容体活性化剤) は,がん細胞の移動と骨転移を誘導する. RANKLを阻害すると,骨における腫瘍負荷が著しく低下し,組織特異的な癌の拡散におけるその役割が強調されます.
科学分野:
- 腫瘍学 腫瘍学
- 細胞生物学 細胞生物学
- 免疫学 免疫学とは
背景:
- 骨転移は,がんの罹患率と痛みの重要な原因です.
- 腫瘍の微小環境,特に骨は,癌の転移に関与しています.
- ケモカインは研究されているが,臓器特異的な転移を調節する他の要因は不明である.
研究 の 目的:
- 癌細胞の移動と骨転移におけるサイトカインRANKL (NF-kappaBリガンドの受容体活性化剤) の役割を調査する.
- 癌細胞のRANKL発現が,癌細胞の転移行動に影響するかどうかを判断する.
- 臨床前モデルのRANKLを標的とした治療の可能性を評価する.
主な方法:
- ヒトがん細胞系および患者由来乳がん細胞のRANK (NF-kappaBの受容体活性化剤) 発現を評価した.
- メラノーマ転移のマウスモデルを利用した.
- オステオプロテゲリンを投与してRANKLを vivoで中和する.
- 腫瘍の負荷と骨や他の器官への転移をモニタリングする.
主要な成果:
- RANKLは,ヒトの上皮がん細胞と,RANKを発現するメラノーマ細胞の移住を誘発する.
- RANKは,様々ながん細胞系と乳がん細胞で発現しています.
- RANKLの vivo 中和は,麻痺からマウスを完全に保護し,骨腫瘍の負担を著しく軽減しましたが,他の臓器ではそうではありません.
結論:
- サイトカインRANKLは,がん細胞の移住を促進する上で重要な役割を果たします.
- RANKLは,癌の組織特異的な骨転移の重要な要因です.
- RANKLをターゲットにすることは,骨転移の管理のための潜在的な治療戦略を提供します.
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