論文 - 詳細
| RRC ID | 87317 |
|---|---|
| 著者 | Eguchi S, Yamada D, Kobayashi S, Sasaki K, Iwagami Y, Yamanaka C, Tomimaru Y, Noda T, Sakaue M, Asaoka T, Shimizu J, Takahashi H, Doki Y, Eguchi H. |
| タイトル | IL-33 released during liver resection facilitates intrahepatic cholangiocarcinoma growth via cytokine secretion in cancer-associated fibroblasts. |
| ジャーナル | Br J Cancer |
| Abstract |
BACKGROUND:We previously reported that IL-33 released during hepatectomy contributes to cytokine-facilitated iCCA tumor growth. However, the underlying mechanisms of the tumor microenvironment remain unexplored. In this study, we aimed to elucidate the impact of IL-33 on cancer-associated fibroblasts (CAFs). METHODS:The abundance of IL-33-positive cells and alpha-SMA-positive fibroblasts (myoCAFs) was evaluated using resected specimens. Next-generation sequencing (NGS) was performed for comprehensive expression analysis. The effects of IL-33 stimulation on CAFs were investigated in vitro and in vivo using human and murine iCCA cell lines, as well as fibroblasts extracted from resected specimens. RESULTS:IL-33-positive cells and myoCAFs were significant risk factors for intrahepatic recurrence. NGS analysis revealed significant upregulation of various cytokines in cases with high number of IL-33-positive cells. The conditioned medium obtained from fibroblasts stimulated with IL-33 enhanced the proliferation and migration of iCCA cell lines. Among the cytokines that were increased by IL-33 stimulation in vitro, IL-6 was suspected to be the dominant. In a murine syngraft model, hepatectomy led to an increased subcutaneous tumor volume by releasing IL-33, whereas IL-6 blockade suppressed this growth. CONCLUSIONS:This study indicated that IL-33 facilitates iCCA growth through fibroblast activation and is associated with intrahepatic recurrence. |
| 巻・号 | 134(3) |
| ページ | 519-529 |
| 公開日 | 2026-2-1 |
| DOI | 10.1038/s41416-025-03256-2 |
| PII | 10.1038/s41416-025-03256-2 |
| PMID | 41276695 |
| PMC | PMC12852916 |
| MeSH | Animals Bile Duct Neoplasms* / metabolism Bile Duct Neoplasms* / pathology Bile Duct Neoplasms* / surgery Cancer-Associated Fibroblasts* / metabolism Cancer-Associated Fibroblasts* / pathology Cell Line, Tumor Cell Movement Cell Proliferation Cholangiocarcinoma* / genetics Cholangiocarcinoma* / metabolism Cholangiocarcinoma* / pathology Cholangiocarcinoma* / surgery Cytokines* / metabolism Female Hepatectomy Humans Interleukin-33* / genetics Interleukin-33* / metabolism Male Mice Middle Aged Tumor Microenvironment |
| IF | 5.791 |
| リソース情報 | |
| ヒト・動物細胞 | SSP-25(RCB1293) RBE(RCB1292) |