CXCL1のパラクリンネットワークは,がんの化学抵抗と転移を結びつける

Swarnali Acharyya¹, Thordur Oskarsson, Sakari Vanharanta

¹Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

Cell

|July 10, 2012

まとめ

新しく発見されたシグナル伝達ネットワークは,癌の転移と化学抵抗を結びつける. この経路をCXCR2阻害剤で標的にすると,乳がんとその拡散に対する化学療法の有効性が向上します.

科学分野:

腫瘍学腫瘍学
がん生物学がん生物学
免疫学免疫学とは

背景:

転移と化学抵抗は,乳がん治療における重要な課題です.
この2つの現象を結びつける分子メカニズムは,ほとんど不明のままである.

研究の目的:

乳がんにおける転移と化学抵抗を結びつける分子基盤を解明する.
これらの課題を克服するための潜在的な治療目標の特定.

主な方法:

癌,骨髄,内皮細胞を含むパラクリンシグナル伝達ネットワークを調査した.
癌の進行と治療への反応におけるケモカインCXCL1/2,S100A8/9,TNF-αの役割を分析した.
化学療法と併用したCXCR2阻害剤の有効性を評価した.

主要な成果:

癌細胞の生存と転移を促進する,骨髄細胞を含むCXCL1/2-S100A8/9シグナリングループを特定しました.
化学療法によってTNF-αの生成が誘発され,このループが増幅され,化学抵抗性がもたらされると実証された.
CXCR2ブロッカーは,このネットワークを破壊し,化学療法の抗腫瘍および抗転移効果を高めることを示しました.

結論:

乳がんの転移と化学抵抗を結びつける新しい内皮がん-骨髄腫信号ネットワークが開発されました.
CXCR2経路を標的にすることは,化学療法の結果を改善し,がんの拡散と戦うために有望な戦略を提供します.

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