CCL20/CXCL5 Drives Crosstalk Between Anaplastic Thyroid Cancer Stem Cells and Tumor‐Associated Macrophages to Promote Tumor Progression

Abstract The dynamic interplay between tumor‐associated macrophages (TAMs) and anaplastic thyroid cancer (ATC) shapes the tumor microenvironment and facilitates ATC progression. However, the mechanisms of communication between TAMs and anaplastic thyroid cancer stem cells (ATCSCs) remain largely une...

Full description

Saved in:
Bibliographic Details
Main Authors: Qi Liu, Yan Wang, Mingyuan Song, Jiapeng Huang, Jinyuan Shi, Wei Sun, Xiaoyu Ji, Yuang Chang, Bing Ma, Ping Zhang, Yuanyuan Yan, Hao Zhang
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202405399
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850039900541288448
author Qi Liu
Yan Wang
Mingyuan Song
Jiapeng Huang
Jinyuan Shi
Wei Sun
Xiaoyu Ji
Yuang Chang
Bing Ma
Ping Zhang
Yuanyuan Yan
Hao Zhang
author_facet Qi Liu
Yan Wang
Mingyuan Song
Jiapeng Huang
Jinyuan Shi
Wei Sun
Xiaoyu Ji
Yuang Chang
Bing Ma
Ping Zhang
Yuanyuan Yan
Hao Zhang
author_sort Qi Liu
collection DOAJ
description Abstract The dynamic interplay between tumor‐associated macrophages (TAMs) and anaplastic thyroid cancer (ATC) shapes the tumor microenvironment and facilitates ATC progression. However, the mechanisms of communication between TAMs and anaplastic thyroid cancer stem cells (ATCSCs) remain largely unelucidated. Integrative analyses of single‐cell RNA sequencing, cytokine/chemokine arrays, proteomics, and mRNA expression datasets are performed to reveal crosstalk between TAMs and ATCSCs and signaling pathways in ATCSCs. Subsequently, in vitro experiments are performed to validate the regulatory effects of key cytokines on ATCSC stemness. Last, xenogeneic orthotopic thyroid ATCSCs transplantation models are utilized to corroborate the regulatory effect of cytokines on stemness. CCL20 derived from THP‐1‐M2 activates the IRAK‐1/NF‐κB1/2 signaling pathway in ATCSCs, thereby positively regulating stemness characteristics and upregulating CXCL5 secretion. ATCSCs not only exhibit autocrine CXCL5 participation in the regulation of stemness but also demonstrate paracrine CXCL5 activity to recruit THP‐1‐Mφ and maintain the M2 phenotype. CCL20 and CXCL5 are involved in the crosstalk between TAMs and ATCSCs. The CCL20/CXCL5 axis plays a crucial role in the interaction between TAMs and ATCSCs, establishing a progressive tumor microenvironment.
format Article
id doaj-art-72c453cdfcd54a75b564f8f760da7a4b
institution DOAJ
issn 2198-3844
language English
publishDate 2025-05-01
publisher Wiley
record_format Article
series Advanced Science
spelling doaj-art-72c453cdfcd54a75b564f8f760da7a4b2025-08-20T02:56:12ZengWileyAdvanced Science2198-38442025-05-011217n/an/a10.1002/advs.202405399CCL20/CXCL5 Drives Crosstalk Between Anaplastic Thyroid Cancer Stem Cells and Tumor‐Associated Macrophages to Promote Tumor ProgressionQi Liu0Yan Wang1Mingyuan Song2Jiapeng Huang3Jinyuan Shi4Wei Sun5Xiaoyu Ji6Yuang Chang7Bing Ma8Ping Zhang9Yuanyuan Yan10Hao Zhang11Department of Thyroid Surgery The First Hospital of China Medical University Shenyang 110801 P. R. ChinaDepartment of Pharmacology School of Pharmacy China Medical University Shenyang 110122 P. R. ChinaDepartment of Thyroid Surgery The First Hospital of China Medical University Shenyang 110801 P. R. ChinaDepartment of Thyroid Surgery The First Hospital of China Medical University Shenyang 110801 P. R. ChinaDepartment of Thyroid Surgery General Surgery Qilu Hospital of Shandong University Jinan 250012 P. R. ChinaDepartment of Thyroid Surgery The First Hospital of China Medical University Shenyang 110801 P. R. ChinaDepartment of Thyroid Surgery The First Hospital of China Medical University Shenyang 110801 P. R. ChinaDepartment of Thyroid Surgery The First Hospital of China Medical University Shenyang 110801 P. R. ChinaDepartment of Clinical Epidemiology and Evidence‐based Medicine The First Hospital of China Medical University Shenyang 110801 P. R. ChinaDepartment of Thyroid Surgery The First Hospital of China Medical University Shenyang 110801 P. R. ChinaDepartment of Pharmacology School of Pharmacy China Medical University Shenyang 110122 P. R. ChinaDepartment of Thyroid Surgery The First Hospital of China Medical University Shenyang 110801 P. R. ChinaAbstract The dynamic interplay between tumor‐associated macrophages (TAMs) and anaplastic thyroid cancer (ATC) shapes the tumor microenvironment and facilitates ATC progression. However, the mechanisms of communication between TAMs and anaplastic thyroid cancer stem cells (ATCSCs) remain largely unelucidated. Integrative analyses of single‐cell RNA sequencing, cytokine/chemokine arrays, proteomics, and mRNA expression datasets are performed to reveal crosstalk between TAMs and ATCSCs and signaling pathways in ATCSCs. Subsequently, in vitro experiments are performed to validate the regulatory effects of key cytokines on ATCSC stemness. Last, xenogeneic orthotopic thyroid ATCSCs transplantation models are utilized to corroborate the regulatory effect of cytokines on stemness. CCL20 derived from THP‐1‐M2 activates the IRAK‐1/NF‐κB1/2 signaling pathway in ATCSCs, thereby positively regulating stemness characteristics and upregulating CXCL5 secretion. ATCSCs not only exhibit autocrine CXCL5 participation in the regulation of stemness but also demonstrate paracrine CXCL5 activity to recruit THP‐1‐Mφ and maintain the M2 phenotype. CCL20 and CXCL5 are involved in the crosstalk between TAMs and ATCSCs. The CCL20/CXCL5 axis plays a crucial role in the interaction between TAMs and ATCSCs, establishing a progressive tumor microenvironment.https://doi.org/10.1002/advs.202405399anaplastic thyroid cancercancer stem cellCCL20crosstalkCXCL5tumor microenvironment
spellingShingle Qi Liu
Yan Wang
Mingyuan Song
Jiapeng Huang
Jinyuan Shi
Wei Sun
Xiaoyu Ji
Yuang Chang
Bing Ma
Ping Zhang
Yuanyuan Yan
Hao Zhang
CCL20/CXCL5 Drives Crosstalk Between Anaplastic Thyroid Cancer Stem Cells and Tumor‐Associated Macrophages to Promote Tumor Progression
Advanced Science
anaplastic thyroid cancer
cancer stem cell
CCL20
crosstalk
CXCL5
tumor microenvironment
title CCL20/CXCL5 Drives Crosstalk Between Anaplastic Thyroid Cancer Stem Cells and Tumor‐Associated Macrophages to Promote Tumor Progression
title_full CCL20/CXCL5 Drives Crosstalk Between Anaplastic Thyroid Cancer Stem Cells and Tumor‐Associated Macrophages to Promote Tumor Progression
title_fullStr CCL20/CXCL5 Drives Crosstalk Between Anaplastic Thyroid Cancer Stem Cells and Tumor‐Associated Macrophages to Promote Tumor Progression
title_full_unstemmed CCL20/CXCL5 Drives Crosstalk Between Anaplastic Thyroid Cancer Stem Cells and Tumor‐Associated Macrophages to Promote Tumor Progression
title_short CCL20/CXCL5 Drives Crosstalk Between Anaplastic Thyroid Cancer Stem Cells and Tumor‐Associated Macrophages to Promote Tumor Progression
title_sort ccl20 cxcl5 drives crosstalk between anaplastic thyroid cancer stem cells and tumor associated macrophages to promote tumor progression
topic anaplastic thyroid cancer
cancer stem cell
CCL20
crosstalk
CXCL5
tumor microenvironment
url https://doi.org/10.1002/advs.202405399
work_keys_str_mv AT qiliu ccl20cxcl5drivescrosstalkbetweenanaplasticthyroidcancerstemcellsandtumorassociatedmacrophagestopromotetumorprogression
AT yanwang ccl20cxcl5drivescrosstalkbetweenanaplasticthyroidcancerstemcellsandtumorassociatedmacrophagestopromotetumorprogression
AT mingyuansong ccl20cxcl5drivescrosstalkbetweenanaplasticthyroidcancerstemcellsandtumorassociatedmacrophagestopromotetumorprogression
AT jiapenghuang ccl20cxcl5drivescrosstalkbetweenanaplasticthyroidcancerstemcellsandtumorassociatedmacrophagestopromotetumorprogression
AT jinyuanshi ccl20cxcl5drivescrosstalkbetweenanaplasticthyroidcancerstemcellsandtumorassociatedmacrophagestopromotetumorprogression
AT weisun ccl20cxcl5drivescrosstalkbetweenanaplasticthyroidcancerstemcellsandtumorassociatedmacrophagestopromotetumorprogression
AT xiaoyuji ccl20cxcl5drivescrosstalkbetweenanaplasticthyroidcancerstemcellsandtumorassociatedmacrophagestopromotetumorprogression
AT yuangchang ccl20cxcl5drivescrosstalkbetweenanaplasticthyroidcancerstemcellsandtumorassociatedmacrophagestopromotetumorprogression
AT bingma ccl20cxcl5drivescrosstalkbetweenanaplasticthyroidcancerstemcellsandtumorassociatedmacrophagestopromotetumorprogression
AT pingzhang ccl20cxcl5drivescrosstalkbetweenanaplasticthyroidcancerstemcellsandtumorassociatedmacrophagestopromotetumorprogression
AT yuanyuanyan ccl20cxcl5drivescrosstalkbetweenanaplasticthyroidcancerstemcellsandtumorassociatedmacrophagestopromotetumorprogression
AT haozhang ccl20cxcl5drivescrosstalkbetweenanaplasticthyroidcancerstemcellsandtumorassociatedmacrophagestopromotetumorprogression