Cancer-Associated Fibroblasts Exposed to High-Dose Ionizing Radiation Promote M2 Polarization of Macrophages, Which Induce Radiosensitivity in Cervical Cancer
Radiotherapy, including brachytherapy, is a major therapeutic regimen for cervical cancer. Radioresistance is a decisive factor in radiation treatment failure. Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) in the tumor microenvironment are critical factors in the curat...
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MDPI AG
2023-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/5/1620 |
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| author | Yuhan Sheng Baofang Zhang Biyuan Xing Zhao Liu Yu Chang Gang Wu Yingchao Zhao |
| author_facet | Yuhan Sheng Baofang Zhang Biyuan Xing Zhao Liu Yu Chang Gang Wu Yingchao Zhao |
| author_sort | Yuhan Sheng |
| collection | DOAJ |
| description | Radiotherapy, including brachytherapy, is a major therapeutic regimen for cervical cancer. Radioresistance is a decisive factor in radiation treatment failure. Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) in the tumor microenvironment are critical factors in the curative effects of cancer therapies. However, the interactions between TAMs and CAFs in the context of ionizing radiation are not fully understood. This study was undertaken to investigate whether M2 macrophages induce radioresistance in cervical cancer and to explore the TAMs’ phenotypic transformation after IR and its underlying mechanisms. The radioresistance of cervical cancer cells was enhanced after being co-cultured with M2 macrophages. TAMs tended to undergo M2 polarization after high-dose irradiation, which was strongly associated with CAFs in both mouse models and patients with cervical cancer. Additionally, cytokine and chemokine analysis was performed to find that high-dose irradiated CAFs promoted macrophage polarization towards the M2 phenotype through chemokine (C-C motif) ligand 2. Collectively, our results highlight the crucial role that high-dose irradiated CAFs play in the regulation of M2 phenotype polarization, which ultimately induces radioresistance in cervical cancer. |
| first_indexed | 2024-03-11T07:29:20Z |
| format | Article |
| id | doaj.art-f9eca4bb7bc746398b4ffc99dcfea30b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T07:29:20Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f9eca4bb7bc746398b4ffc99dcfea30b2023-11-17T07:26:37ZengMDPI AGCancers2072-66942023-03-01155162010.3390/cancers15051620Cancer-Associated Fibroblasts Exposed to High-Dose Ionizing Radiation Promote M2 Polarization of Macrophages, Which Induce Radiosensitivity in Cervical CancerYuhan Sheng0Baofang Zhang1Biyuan Xing2Zhao Liu3Yu Chang4Gang Wu5Yingchao Zhao6Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 420022, ChinaCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 420022, ChinaCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 420022, ChinaCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 420022, ChinaCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 420022, ChinaCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 420022, ChinaCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 420022, ChinaRadiotherapy, including brachytherapy, is a major therapeutic regimen for cervical cancer. Radioresistance is a decisive factor in radiation treatment failure. Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) in the tumor microenvironment are critical factors in the curative effects of cancer therapies. However, the interactions between TAMs and CAFs in the context of ionizing radiation are not fully understood. This study was undertaken to investigate whether M2 macrophages induce radioresistance in cervical cancer and to explore the TAMs’ phenotypic transformation after IR and its underlying mechanisms. The radioresistance of cervical cancer cells was enhanced after being co-cultured with M2 macrophages. TAMs tended to undergo M2 polarization after high-dose irradiation, which was strongly associated with CAFs in both mouse models and patients with cervical cancer. Additionally, cytokine and chemokine analysis was performed to find that high-dose irradiated CAFs promoted macrophage polarization towards the M2 phenotype through chemokine (C-C motif) ligand 2. Collectively, our results highlight the crucial role that high-dose irradiated CAFs play in the regulation of M2 phenotype polarization, which ultimately induces radioresistance in cervical cancer.https://www.mdpi.com/2072-6694/15/5/1620cervical cancerradiotherapyradioresistancetumor-associated macrophagescancer-associated fibroblasts |
| spellingShingle | Yuhan Sheng Baofang Zhang Biyuan Xing Zhao Liu Yu Chang Gang Wu Yingchao Zhao Cancer-Associated Fibroblasts Exposed to High-Dose Ionizing Radiation Promote M2 Polarization of Macrophages, Which Induce Radiosensitivity in Cervical Cancer Cancers cervical cancer radiotherapy radioresistance tumor-associated macrophages cancer-associated fibroblasts |
| title | Cancer-Associated Fibroblasts Exposed to High-Dose Ionizing Radiation Promote M2 Polarization of Macrophages, Which Induce Radiosensitivity in Cervical Cancer |
| title_full | Cancer-Associated Fibroblasts Exposed to High-Dose Ionizing Radiation Promote M2 Polarization of Macrophages, Which Induce Radiosensitivity in Cervical Cancer |
| title_fullStr | Cancer-Associated Fibroblasts Exposed to High-Dose Ionizing Radiation Promote M2 Polarization of Macrophages, Which Induce Radiosensitivity in Cervical Cancer |
| title_full_unstemmed | Cancer-Associated Fibroblasts Exposed to High-Dose Ionizing Radiation Promote M2 Polarization of Macrophages, Which Induce Radiosensitivity in Cervical Cancer |
| title_short | Cancer-Associated Fibroblasts Exposed to High-Dose Ionizing Radiation Promote M2 Polarization of Macrophages, Which Induce Radiosensitivity in Cervical Cancer |
| title_sort | cancer associated fibroblasts exposed to high dose ionizing radiation promote m2 polarization of macrophages which induce radiosensitivity in cervical cancer |
| topic | cervical cancer radiotherapy radioresistance tumor-associated macrophages cancer-associated fibroblasts |
| url | https://www.mdpi.com/2072-6694/15/5/1620 |
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