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...
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Wiley
2025-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202405399 |
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| 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 |
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