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Tumor-associated macrophages promote pancreatic ductal adenocarcinoma progression by inducing epithelial-to-mesenchymal transition

In this study, we investigated the role of tumor-associated macrophages (TAMs) in the progression of pancreatic ductal adenocarcinoma (PDAC). PDAC patients with higher levels of CD68(+) TAMs exhibited shorter overall survival. In Transwell assays, PDAC cells incubated with TAMs or conditioned media...

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Autores principales: Xiong, Cheng, Zhu, Youwei, Xue, Meilin, Jiang, Yongsheng, Zhong, Yiming, Jiang, Lingxi, Shi, Minmin, Chen, Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906203/
https://www.ncbi.nlm.nih.gov/pubmed/33428605
http://dx.doi.org/10.18632/aging.202264
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author Xiong, Cheng
Zhu, Youwei
Xue, Meilin
Jiang, Yongsheng
Zhong, Yiming
Jiang, Lingxi
Shi, Minmin
Chen, Hao
author_facet Xiong, Cheng
Zhu, Youwei
Xue, Meilin
Jiang, Yongsheng
Zhong, Yiming
Jiang, Lingxi
Shi, Minmin
Chen, Hao
author_sort Xiong, Cheng
collection PubMed
description In this study, we investigated the role of tumor-associated macrophages (TAMs) in the progression of pancreatic ductal adenocarcinoma (PDAC). PDAC patients with higher levels of CD68(+) TAMs exhibited shorter overall survival. In Transwell assays, PDAC cells incubated with TAMs or conditioned media from TAM cells (TAM-CM) showed higher migration and invasion rates than controls. PET/CT scan analysis of orthotopic PDAC model mice revealed greater primary tumor growth and liver metastasis in the TAM-CM treatment group than the controls. H&E staining of liver tissues showed significantly higher numbers of metastatic nodules in the TAM-CM treatment group. Heat inactivation of TAM-CM significantly reduced Transwell migration by PDAC cells, suggesting the involvement of one or more secreted proteins in PDAC progression. Transcriptome sequencing analysis of PDAC cells treated with TAM-CM revealed significant enrichment of transforming growth factor-β (TGF-β) signaling pathway genes. Western blot and qRT-PCR analysis showed that TAM-CM enhanced PDAC migration cells by inducing epithelial-to-mesenchymal transition through the TGF-β-Smad2/3/4-Snail signaling axis. The pro-tumorigenic effects of TAMs or TAM-CM were abolished by TGF-β signaling pathway inhibitors and neutralizing TGF-β antibody. These results demonstrate that TAMs promote PDAC progression through the TGF-β signaling pathway.
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spelling pubmed-79062032021-03-04 Tumor-associated macrophages promote pancreatic ductal adenocarcinoma progression by inducing epithelial-to-mesenchymal transition Xiong, Cheng Zhu, Youwei Xue, Meilin Jiang, Yongsheng Zhong, Yiming Jiang, Lingxi Shi, Minmin Chen, Hao Aging (Albany NY) Research Paper In this study, we investigated the role of tumor-associated macrophages (TAMs) in the progression of pancreatic ductal adenocarcinoma (PDAC). PDAC patients with higher levels of CD68(+) TAMs exhibited shorter overall survival. In Transwell assays, PDAC cells incubated with TAMs or conditioned media from TAM cells (TAM-CM) showed higher migration and invasion rates than controls. PET/CT scan analysis of orthotopic PDAC model mice revealed greater primary tumor growth and liver metastasis in the TAM-CM treatment group than the controls. H&E staining of liver tissues showed significantly higher numbers of metastatic nodules in the TAM-CM treatment group. Heat inactivation of TAM-CM significantly reduced Transwell migration by PDAC cells, suggesting the involvement of one or more secreted proteins in PDAC progression. Transcriptome sequencing analysis of PDAC cells treated with TAM-CM revealed significant enrichment of transforming growth factor-β (TGF-β) signaling pathway genes. Western blot and qRT-PCR analysis showed that TAM-CM enhanced PDAC migration cells by inducing epithelial-to-mesenchymal transition through the TGF-β-Smad2/3/4-Snail signaling axis. The pro-tumorigenic effects of TAMs or TAM-CM were abolished by TGF-β signaling pathway inhibitors and neutralizing TGF-β antibody. These results demonstrate that TAMs promote PDAC progression through the TGF-β signaling pathway. Impact Journals 2021-01-10 /pmc/articles/PMC7906203/ /pubmed/33428605 http://dx.doi.org/10.18632/aging.202264 Text en Copyright: © 2021 Xiong et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Xiong, Cheng
Zhu, Youwei
Xue, Meilin
Jiang, Yongsheng
Zhong, Yiming
Jiang, Lingxi
Shi, Minmin
Chen, Hao
Tumor-associated macrophages promote pancreatic ductal adenocarcinoma progression by inducing epithelial-to-mesenchymal transition
title Tumor-associated macrophages promote pancreatic ductal adenocarcinoma progression by inducing epithelial-to-mesenchymal transition
title_full Tumor-associated macrophages promote pancreatic ductal adenocarcinoma progression by inducing epithelial-to-mesenchymal transition
title_fullStr Tumor-associated macrophages promote pancreatic ductal adenocarcinoma progression by inducing epithelial-to-mesenchymal transition
title_full_unstemmed Tumor-associated macrophages promote pancreatic ductal adenocarcinoma progression by inducing epithelial-to-mesenchymal transition
title_short Tumor-associated macrophages promote pancreatic ductal adenocarcinoma progression by inducing epithelial-to-mesenchymal transition
title_sort tumor-associated macrophages promote pancreatic ductal adenocarcinoma progression by inducing epithelial-to-mesenchymal transition
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906203/
https://www.ncbi.nlm.nih.gov/pubmed/33428605
http://dx.doi.org/10.18632/aging.202264
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