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膵腫瘍内の歯周病菌 Fusobacterium nucleatum はCXCL1―CXCR2シグナルを介して膵癌の進展を促進する

林, 昌孝 HAYASHI, Masataka ハヤシ, マサタカ 九州大学

2023.09.25

概要

九州大学学術情報リポジトリ
Kyushu University Institutional Repository

Intratumor Fusobacterium nucleatum promotes the
progression of pancreatic cancer via the CXCL1CXCR2 axis
林, 昌孝

https://hdl.handle.net/2324/7157308
出版情報:Kyushu University, 2023, 博士(医学), 課程博士
バージョン:
権利関係:Creative Commons Attribution-NonCommercial International

氏 名:

林 昌孝

論文名:

Intratumor Fusobacterium nucleatum promotes the progression of pancreatic
cancer via the CXCL1-CXCR2 axis
(膵腫瘍内の歯周病菌 Fusobacterium nucleatum はCXCL1―CXCR2シグナルを介して
膵癌の進展を促進する)

区 分:



論 文 内 容 の 要 旨

 Fusobacterium nucleatum (F.nucleatum )は歯周病の原因となる嫌気性菌のひとつである。
Fusobacterium を膵腫瘍内で検出する症例では予後不良と報告されており、F.nucleatum が癌微小環
境の一員として膵癌の進展を促進する可能性があるが、そのメカニズムは解明されていない。本研究
の目的は、膵腫瘍内のF.nucleatum が膵癌の進展に及ぼす影響を明らかにすることである。ヒト膵切
除組織からDNAを抽出し、F.nucleatum 由来のDNA発現量をPCRで評価した。膵腫瘍内のF.nucleatum は
正常膵組織より多く検出し、腫瘍内F.nucleatum 検出群は非検出群と比較して、腫瘍径が大きく、全
生存期間が短縮していた。F.nucleatum は、膵癌細胞の遊走能と浸潤能を促進し、膵癌細胞のCXCL1産
生を促進した。CXCL1の受容体であるCXCR2を阻害すると、F.nucleatum により促進した膵癌細胞の遊
走能が抑制された。膵癌自然発生マウス由来の膵癌細胞株皮下移植モデルにF.nucleatum を腫瘍内へ
投与した実験では、F.nucleatum 腫瘍内投与群では、腫瘍の増大を認め、骨髄由来免疫抑制細胞
(MDSC) が増加し、CD8陽性T細胞が減少した。抗CXCL1抗体、CXCR2 阻害剤、MDSC阻害剤による治療実
験では、いずれもF.nucleatum により増大した腫瘍が抑制された。以上の結果から、膵腫瘍内の
F.nucleatum は癌細胞のCXCL1産生を促進し、癌細胞自身や腫瘍内の免疫細胞を改変することで、癌の
進展を促進することが示唆された。本研究は、腫瘍内にF.nucleatum が存在する膵癌患者に対する新
しい治療戦略となる可能性がある。

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S U P P O R T I N G I N FO R M AT I O N

Additional supporting information can be found online in the

Supporting Information section at the end of this article.

How to cite this article: Hayashi M, Ikenaga N, Nakata K,

et al. Intratumor Fusobacterium nucleatum promotes the

progression of pancreatic cancer via the CXCL1-­CXCR2 axis.

Cancer Sci. 2023;00:1-13. doi:10.1111/cas.15901

13497006, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cas.15901 by Cochrane Japan, Wiley Online Library on [14/07/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

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