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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Elsevier
2025-01-01
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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 |
id | doaj-art-0fd7c31eec194b06bb6474637f366ac6 |
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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