カルシノマ産生因子は,TLR2を通じて骨髄細胞を活性化し,転移を刺激する

Sunhwa Kim¹, Hiroyuki Takahashi, Wan-Wan Lin

¹Department of Pharmacology and Cancer Center, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA.

Nature

|January 6, 2009

まとめ

ルイス肺がん (LLC) のような進行がん細胞は,versicanを分泌する. この分子は,トール型受容体 (TLR) を介してマクロファージを活性化し,炎症を促進し,腫瘍転移を促進します.

科学分野:

腫瘍学腫瘍学
免疫学免疫学とは
バイオケミストリーバイオケミストリー

背景:

転移性進行は,がん細胞遺伝学と腫瘍マイクロ環境の炎症の影響を受けます.
炎症性マイクロ環境に対する癌細胞の影響を理解することは極めて重要です.

研究の目的:

転移性癌によって分泌されるマクロファージ活性化因子を特定するために.
転移を促進するこれらの要因の役割を明らかにする.

主な方法:

転移性ルイス肺がん (LLC) 細胞系からのマクロファージ活性化因子の生化学的スクリーニング.
LLCで調節された媒体の浄化によるヴァルシカンの識別.
マクロファージの活性化と転移におけるトール型受容体 (TLR) の関与の分析.

主要な成果:

ルイス肺がん (LLC) 細胞はマクロファージを強力に活性化し,TLR2とTLR6経由でインタールイキン-6 (IL-6) と腫瘍死滅因子アルファ (TNF-alpha) を誘導します.
TNF-αとTLR2の両方が,LLCの転移に不可欠でした.
細胞外マトリックスプロテオグリカン・ヴァルシカンは,TLR2:TLR6複合体とCD14を通じて作用する重要なマクロファージ活性化剤として特定されました.
ヴェルシカンは,ミエロイド細胞からTNF-αの分泌を誘導することによって,LLCの転移的成長を強化しました.

結論:

先進的な癌細胞は,先天的な免疫システム成分を乗っ取り,プロ転移性炎症性マイクロ環境を促進します.
癌細胞によって分泌されるヴェルシカンは,骨髄細胞を活性化し,炎症を誘発することにより,転移を促進する上で重要な役割を果たします.

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