Neutrophil extracellular traps promote cancer-associated inflammation and myocardial stress
Cancer is associated with systemic pathologies that contribute to mortality, such as thrombosis and distant organ failure. The aim of this study was to investigate the potential role of neutrophil extracellular traps (NETs) in myocardial inflammation and tissue damage in treatment-naïve individuals...
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| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2022.2049487 |
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| author | J. Cedervall M. Herre A. Dragomir F. Rabelo-Melo A. Svensson C. Thålin A. Rosell V. Hjalmar H. Wallén H. Lindman G. Pejler E. Hagström M. Hultström A. Larsson AK. Olsson |
| author_facet | J. Cedervall M. Herre A. Dragomir F. Rabelo-Melo A. Svensson C. Thålin A. Rosell V. Hjalmar H. Wallén H. Lindman G. Pejler E. Hagström M. Hultström A. Larsson AK. Olsson |
| author_sort | J. Cedervall |
| collection | DOAJ |
| description | Cancer is associated with systemic pathologies that contribute to mortality, such as thrombosis and distant organ failure. The aim of this study was to investigate the potential role of neutrophil extracellular traps (NETs) in myocardial inflammation and tissue damage in treatment-naïve individuals with cancer. Mice with mammary carcinoma (MMTV-PyMT) had increased plasma levels of NETs measured as H3Cit-DNA complexes, paralleled with elevated coagulation, compared to healthy littermates. MMTV-PyMT mice displayed upregulation of pro-inflammatory markers in the heart, myocardial hypertrophy and elevated cardiac disease biomarkers in the blood, but not echocardiographic heart failure. Moreover, increased endothelial proliferation was observed in hearts from tumor-bearing mice. Removal of NETs by DNase I treatment suppressed the myocardial inflammation, expression of cardiac disease biomarkers and endothelial proliferation. Compared to a healthy control group, treatment-naïve cancer patients with different malignant disorders had increased NET formation, which correlated to plasma levels of the inflammatory marker CRP and the cardiac disease biomarkers NT-proBNP and sTNFR1, in agreement with the mouse data. Altogether, our data indicate that NETs contribute to inflammation and myocardial stress during malignancy. These findings suggest NETs as potential therapeutic targets to prevent cardiac inflammation and dysfunction in cancer patients. |
| format | Article |
| id | doaj-art-34187af0dbf445fb9bafb39e14648dd2 |
| institution | DOAJ |
| issn | 2162-402X |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-34187af0dbf445fb9bafb39e14648dd22025-08-20T03:01:50ZengTaylor & Francis GroupOncoImmunology2162-402X2022-12-0111110.1080/2162402X.2022.2049487Neutrophil extracellular traps promote cancer-associated inflammation and myocardial stressJ. Cedervall0M. Herre1A. Dragomir2F. Rabelo-Melo3A. Svensson4C. Thålin5A. Rosell6V. Hjalmar7H. Wallén8H. Lindman9G. Pejler10E. Hagström11M. Hultström12A. Larsson13AK. Olsson14Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Uppsala, SwedenDepartment of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, SwedenDepartment of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Uppsala, SwedenDepartment of Medical Cell Biology, Integrative Physiology, Uppsala University, Uppsala, SwedenDepartment of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, SwedenDepartment of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, SwedenDepartment of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, SwedenDepartment of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, SwedenDepartment of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Uppsala, SwedenDepartment of Medical Sciences, Uppsala University, Uppsala, SwedenDepartment of Medical Cell Biology, Integrative Physiology, Uppsala University, Uppsala, SwedenDepartment of Medical Sciences, Uppsala University, Uppsala, SwedenDepartment of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Uppsala, SwedenCancer is associated with systemic pathologies that contribute to mortality, such as thrombosis and distant organ failure. The aim of this study was to investigate the potential role of neutrophil extracellular traps (NETs) in myocardial inflammation and tissue damage in treatment-naïve individuals with cancer. Mice with mammary carcinoma (MMTV-PyMT) had increased plasma levels of NETs measured as H3Cit-DNA complexes, paralleled with elevated coagulation, compared to healthy littermates. MMTV-PyMT mice displayed upregulation of pro-inflammatory markers in the heart, myocardial hypertrophy and elevated cardiac disease biomarkers in the blood, but not echocardiographic heart failure. Moreover, increased endothelial proliferation was observed in hearts from tumor-bearing mice. Removal of NETs by DNase I treatment suppressed the myocardial inflammation, expression of cardiac disease biomarkers and endothelial proliferation. Compared to a healthy control group, treatment-naïve cancer patients with different malignant disorders had increased NET formation, which correlated to plasma levels of the inflammatory marker CRP and the cardiac disease biomarkers NT-proBNP and sTNFR1, in agreement with the mouse data. Altogether, our data indicate that NETs contribute to inflammation and myocardial stress during malignancy. These findings suggest NETs as potential therapeutic targets to prevent cardiac inflammation and dysfunction in cancer patients.https://www.tandfonline.com/doi/10.1080/2162402X.2022.2049487Neutrophil extracellular trapsNETscancercardiachypertrophyinflammation |
| spellingShingle | J. Cedervall M. Herre A. Dragomir F. Rabelo-Melo A. Svensson C. Thålin A. Rosell V. Hjalmar H. Wallén H. Lindman G. Pejler E. Hagström M. Hultström A. Larsson AK. Olsson Neutrophil extracellular traps promote cancer-associated inflammation and myocardial stress OncoImmunology Neutrophil extracellular traps NETs cancer cardiac hypertrophy inflammation |
| title | Neutrophil extracellular traps promote cancer-associated inflammation and myocardial stress |
| title_full | Neutrophil extracellular traps promote cancer-associated inflammation and myocardial stress |
| title_fullStr | Neutrophil extracellular traps promote cancer-associated inflammation and myocardial stress |
| title_full_unstemmed | Neutrophil extracellular traps promote cancer-associated inflammation and myocardial stress |
| title_short | Neutrophil extracellular traps promote cancer-associated inflammation and myocardial stress |
| title_sort | neutrophil extracellular traps promote cancer associated inflammation and myocardial stress |
| topic | Neutrophil extracellular traps NETs cancer cardiac hypertrophy inflammation |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2022.2049487 |
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