Tumor-associated macrophages contribute to cholangiocarcinoma progression and chemoresistance through activation of ID1.

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Annals of hepatology Pub Date : 2024-12-12 DOI:10.1016/j.aohep.2024.101773

Yinghao Guo, Shuangda Miao, Yun Jin, Qi Li, Yihang Wang, Xiaoxiao Zhang, Jiangtao Li

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Abstract

Introduction and objectives: Tumor-associated macrophages (TAM) can influence both cancer growth and chemoresistance, but the specific mechanisms involved in these processes in cholangiocarcinoma (CCA) are unclear.

Materials and methods: We explored the distribution of TAM in CCA samples by multiplex immunofluorescence staining and tested the effects of TAM on CCA in vitro and in vivo. We then investigated the mechanisms underlying these effects using the Luminex assay, RNA sequencing, western blotting, flow cytometry, and co-immunoprecipitation.

Results: The infiltration of TAM was strongly increased in the cholangiocarcinoma tumor microenvironment. Oncostain M (OSM) secreted by TAM increased the proliferation and chemotherapeutic resistance of CCA cells both in vitro and in vivo. The results of transcriptome sequencing analysis, Western blot analysis, and immunofluorescence staining confirmed that OSM can promote Yap nuclear translocation and its subsequent formation of complexes with SMADs to upregulate the expression of inhibitor of DNA binding 1 (ID1).

Conclusions: TAM promotes CCA progression and chemoresistance through activating OSM-Yap-ID1.

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肿瘤相关巨噬细胞通过激活 ID1 促进了胆管癌的发展和化疗耐药性。

简介和目的：肿瘤相关巨噬细胞（TAM）可以影响肿瘤生长和化疗耐药，但在胆管癌（CCA）中参与这些过程的具体机制尚不清楚。材料与方法：采用多重免疫荧光染色法研究TAM在CCA样品中的分布，并在体外和体内检测TAM对CCA的影响。然后，我们使用Luminex测定、RNA测序、western blotting、流式细胞术和共免疫沉淀研究了这些作用的机制。结果：胆管癌肿瘤微环境中TAM的浸润明显增加。TAM分泌的Oncostain M （OSM）在体外和体内均能增加CCA细胞的增殖和化疗耐药性。转录组测序分析、Western blot分析和免疫荧光染色结果证实，OSM可以促进Yap核易位及其随后与SMADs形成复合物，上调DNA结合抑制剂1 （inhibitor of DNA binding 1, ID1）的表达。结论：TAM通过激活OSM-Yap-ID1促进CCA进展和化疗耐药。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of hepatology 医学-胃肠肝病学

CiteScore

7.90

自引率

2.60%

发文量

183

审稿时长

4-8 weeks

期刊介绍： Annals of Hepatology publishes original research on the biology and diseases of the liver in both humans and experimental models. Contributions may be submitted as regular articles. The journal also publishes concise reviews of both basic and clinical topics.