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大学・研究所にある論文を検索できる 「癌性腹水・胸水中のマクロファージは線維芽細胞へ分化転換する」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

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癌性腹水・胸水中のマクロファージは線維芽細胞へ分化転換する

伊東, 守 ITO, Mamoru イトウ, マモル 九州大学

2022.10.31

概要

がん関連線維芽細胞(cancer-associated fibroblast: CAF)は、がんの進行に重要な役割を担っている。しかし、CAFの起源は未だ不明である。本研究では、癌性腹水や胸水中のマクロファージ(cavityfluid-associated macrophage: CAM)が線維芽細胞様細胞へ直接分化転換することを明らかにした。消化器癌患者から得られたCAMをフローサイトメトリーで選別し、invitroで培養するとCD45+CD14+CAMは、紡錘形を呈するCD45-CD90+線維芽細胞様細胞へ分化転換した。cDNAマイクロアレイ解析により、このCD45-CD90+線維芽細胞様細胞(macrophage-derived CAF: MDCAF)は線維芽細胞に特異的な遺伝子発現を持ち、上皮細胞を発育させる増殖因子を産生することが示された。MDCAFをヒト大腸がん細胞株と免疫不全マウスに共移植することで、がん細胞のみを移植するよりも大きな腫瘍を形成した。遺伝子オントロジー解析により、MDCAFにはTGFβシグナルと細胞-マトリックス接着が関与しており、TGF βと細胞接着を阻害することでCAMのMDCAFへの分化転換が抑制されることが示された。さらに、造血幹細胞(hematopoietic stem cell: HSC)に生じた体細胞遺伝子変異は、CAMとMDCAFに引き継がれており、このことからCAMはCAFの供給源であり,かつ造血幹細胞を起源とする可能性が示された。以上からCAMからMDCAFへの分化転換を阻害することが、消化器癌に伴う線維化を標的とした新たな治療戦略となる可能性がある。

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