Radiation-induced rescue effect on human breast carcinoma cells is regulated by macrophages
The susceptibility of cancer cells to DNA damages is influenced by their microenvironment. For example, unirradiated neighbors of irradiated cells can produce signals that reduce DNA damages. This phenomenon, known as Radiation-Induced Rescue Effect (RIRE), has profound implications on the efficacy...
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Elsevier
2025-03-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580825000238 |
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| author | Spoorthy Pathikonda Li Tian Clement Manohar Arava Shuk Han Cheng Yun Wah Lam |
| author_facet | Spoorthy Pathikonda Li Tian Clement Manohar Arava Shuk Han Cheng Yun Wah Lam |
| author_sort | Spoorthy Pathikonda |
| collection | DOAJ |
| description | The susceptibility of cancer cells to DNA damages is influenced by their microenvironment. For example, unirradiated neighbors of irradiated cells can produce signals that reduce DNA damages. This phenomenon, known as Radiation-Induced Rescue Effect (RIRE), has profound implications on the efficacy of radiotherapy. Using bystander cells co-cultured with mock-irradiated cells as a control, we demonstrated, for the first time, two types of RIRE. Conditioned medium from naïve by stander cells, i.e., cells not exposed to irradiated cells, could mitigate UV-induced DNA damages in human breast carcinoma MCF7 cells, as judged by phospho-H2AX and 53BP1 immunostaining. This protective effect could be further enhanced by the prior treatment of bystander cells with factors from UV-irradiated cells. We named the former effect “basal RIRE” and the latter “active RIRE” which were cell type-dependent. As bystanders, MCF7 showed a significant active RIRE, whereas THP1-derived macrophages showed a strong basal RIRE but no active RIRE. Interestingly, RIRE of macrophages could further be modulated by polarisation. The basal RIRE of macrophages was abolished by M1 polarisation, while M2 and Tumour Associated Macrophages (TAM) demonstrated pronounced basal and active RIRE. When mixtures of MCF7 cells and polarised macrophages were used as bystanders, the overall RIRE was dictated by macrophage phenotypes: RIRE was suppressed by M1 macrophages but significantly enhanced by M2 and TAM. This study shows a previously unappreciated role of the innate immune system in RIRE. Depending on polarised phenotypes, macrophages in the tumour microenvironment can interfere with the effectiveness of radiotherapy by adjusting the RIRE magnitudes. |
| format | Article |
| id | doaj-art-1c13b4cd39544f2e9a121c1c3a924ad6 |
| institution | Kabale University |
| issn | 2405-5808 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj-art-1c13b4cd39544f2e9a121c1c3a924ad62025-02-09T05:00:37ZengElsevierBiochemistry and Biophysics Reports2405-58082025-03-0141101936Radiation-induced rescue effect on human breast carcinoma cells is regulated by macrophagesSpoorthy Pathikonda0Li Tian1Clement Manohar Arava2Shuk Han Cheng3Yun Wah Lam4Departments of Chemistry, City University of Hong Kong, Kowloon Tong, Hong Kong Special Administrative Region of ChinaDepartments of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong Special Administrative Region of ChinaLaboratoire Sciences et Méthodes Séparatives, Université de Rouen Normandie, Rouen, FranceDepartments of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong Special Administrative Region of ChinaDepartments of Chemistry, City University of Hong Kong, Kowloon Tong, Hong Kong Special Administrative Region of China; School of Applied Sciences, University of Huddersfield, Huddersfield, UK; Corresponding author. Department of Chemistry, City University of Hong Kong, Kowloon Tong, Hong Kong Special Administrative Region of China.The susceptibility of cancer cells to DNA damages is influenced by their microenvironment. For example, unirradiated neighbors of irradiated cells can produce signals that reduce DNA damages. This phenomenon, known as Radiation-Induced Rescue Effect (RIRE), has profound implications on the efficacy of radiotherapy. Using bystander cells co-cultured with mock-irradiated cells as a control, we demonstrated, for the first time, two types of RIRE. Conditioned medium from naïve by stander cells, i.e., cells not exposed to irradiated cells, could mitigate UV-induced DNA damages in human breast carcinoma MCF7 cells, as judged by phospho-H2AX and 53BP1 immunostaining. This protective effect could be further enhanced by the prior treatment of bystander cells with factors from UV-irradiated cells. We named the former effect “basal RIRE” and the latter “active RIRE” which were cell type-dependent. As bystanders, MCF7 showed a significant active RIRE, whereas THP1-derived macrophages showed a strong basal RIRE but no active RIRE. Interestingly, RIRE of macrophages could further be modulated by polarisation. The basal RIRE of macrophages was abolished by M1 polarisation, while M2 and Tumour Associated Macrophages (TAM) demonstrated pronounced basal and active RIRE. When mixtures of MCF7 cells and polarised macrophages were used as bystanders, the overall RIRE was dictated by macrophage phenotypes: RIRE was suppressed by M1 macrophages but significantly enhanced by M2 and TAM. This study shows a previously unappreciated role of the innate immune system in RIRE. Depending on polarised phenotypes, macrophages in the tumour microenvironment can interfere with the effectiveness of radiotherapy by adjusting the RIRE magnitudes.http://www.sciencedirect.com/science/article/pii/S2405580825000238Radiation-induced rescue effect (RIRE)M1/M2 macrophagesTumour-associated macrophages (TAMs)DNA damageUV |
| spellingShingle | Spoorthy Pathikonda Li Tian Clement Manohar Arava Shuk Han Cheng Yun Wah Lam Radiation-induced rescue effect on human breast carcinoma cells is regulated by macrophages Biochemistry and Biophysics Reports Radiation-induced rescue effect (RIRE) M1/M2 macrophages Tumour-associated macrophages (TAMs) DNA damage UV |
| title | Radiation-induced rescue effect on human breast carcinoma cells is regulated by macrophages |
| title_full | Radiation-induced rescue effect on human breast carcinoma cells is regulated by macrophages |
| title_fullStr | Radiation-induced rescue effect on human breast carcinoma cells is regulated by macrophages |
| title_full_unstemmed | Radiation-induced rescue effect on human breast carcinoma cells is regulated by macrophages |
| title_short | Radiation-induced rescue effect on human breast carcinoma cells is regulated by macrophages |
| title_sort | radiation induced rescue effect on human breast carcinoma cells is regulated by macrophages |
| topic | Radiation-induced rescue effect (RIRE) M1/M2 macrophages Tumour-associated macrophages (TAMs) DNA damage UV |
| url | http://www.sciencedirect.com/science/article/pii/S2405580825000238 |
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