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

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 multiple...

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Main Authors: Yinghao Guo, Shuangda Miao, Yun Jin, Qi Li, Yihang Wang, Xiaoxiao Zhang, Jiangtao Li
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Annals of Hepatology
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Online Access:http://www.sciencedirect.com/science/article/pii/S1665268124005568
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author Yinghao Guo
Shuangda Miao
Yun Jin
Qi Li
Yihang Wang
Xiaoxiao Zhang
Jiangtao Li
author_facet Yinghao Guo
Shuangda Miao
Yun Jin
Qi Li
Yihang Wang
Xiaoxiao Zhang
Jiangtao Li
author_sort Yinghao Guo
collection DOAJ
description 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.
format Article
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institution Kabale University
issn 1665-2681
language English
publishDate 2025-01-01
publisher Elsevier
record_format Article
series Annals of Hepatology
spelling doaj-art-0fd7c31eec194b06bb6474637f366ac62025-01-05T04:27:53ZengElsevierAnnals of Hepatology1665-26812025-01-01301101773Tumor-associated macrophages contribute to cholangiocarcinoma progression and chemoresistance through activation of ID1Yinghao Guo0Shuangda Miao1Yun Jin2Qi Li3Yihang Wang4Xiaoxiao Zhang5Jiangtao Li6Department of Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, ChinaDepartment of Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, ChinaDepartment of Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, ChinaDepartment of Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, ChinaDepartment of Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, ChinaDepartment of Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, ChinaCorresponding author.; Department of Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, ChinaIntroduction 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.http://www.sciencedirect.com/science/article/pii/S1665268124005568CholangiocarcinomaTumor-associated macrophageInhibitor of DNA binding 1Oncostatin M
spellingShingle Yinghao Guo
Shuangda Miao
Yun Jin
Qi Li
Yihang Wang
Xiaoxiao Zhang
Jiangtao Li
Tumor-associated macrophages contribute to cholangiocarcinoma progression and chemoresistance through activation of ID1
Annals of Hepatology
Cholangiocarcinoma
Tumor-associated macrophage
Inhibitor of DNA binding 1
Oncostatin M
title Tumor-associated macrophages contribute to cholangiocarcinoma progression and chemoresistance through activation of ID1
title_full Tumor-associated macrophages contribute to cholangiocarcinoma progression and chemoresistance through activation of ID1
title_fullStr Tumor-associated macrophages contribute to cholangiocarcinoma progression and chemoresistance through activation of ID1
title_full_unstemmed Tumor-associated macrophages contribute to cholangiocarcinoma progression and chemoresistance through activation of ID1
title_short Tumor-associated macrophages contribute to cholangiocarcinoma progression and chemoresistance through activation of ID1
title_sort tumor associated macrophages contribute to cholangiocarcinoma progression and chemoresistance through activation of id1
topic Cholangiocarcinoma
Tumor-associated macrophage
Inhibitor of DNA binding 1
Oncostatin M
url http://www.sciencedirect.com/science/article/pii/S1665268124005568
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