IL-1β Blockade Attenuates Thrombosis in a Neutrophil Extracellular Trap-Dependent Breast Cancer Model
Cancer patients are at increased risk of developing thrombosis, comorbidity that has been associated with increased neutrophil counts and the formation of neutrophil extracellular traps (NETs). Interleukin-1β (IL-1β) modulates the expression of granulocyte colony-stimulating factor (G-CSF), a cytoki...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02088/full |
| _version_ | 1818503189483225088 |
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| author | Tainá Gomes Carolina B. S. Várady André L. Lourenço Daniella M. Mizurini Araci M. R. Rondon Ana C. Leal Barbara S. Gonçalves Dumith Chequer Bou-Habib Dumith Chequer Bou-Habib Emiliano Medei Robson Q. Monteiro |
| author_facet | Tainá Gomes Carolina B. S. Várady André L. Lourenço Daniella M. Mizurini Araci M. R. Rondon Ana C. Leal Barbara S. Gonçalves Dumith Chequer Bou-Habib Dumith Chequer Bou-Habib Emiliano Medei Robson Q. Monteiro |
| author_sort | Tainá Gomes |
| collection | DOAJ |
| description | Cancer patients are at increased risk of developing thrombosis, comorbidity that has been associated with increased neutrophil counts and the formation of neutrophil extracellular traps (NETs). Interleukin-1β (IL-1β) modulates the expression of granulocyte colony-stimulating factor (G-CSF), a cytokine that promotes cancer-associated neutrophilia and NET generation. Herein, we combined a murine breast cancer model with a flow-restriction thrombosis model to evaluate whether the IL-1β blockade could interfere with cancer-associated thrombosis. Mice bearing metastatic 4T1 tumors exhibited high neutrophil counts as well as elevated expression of G-CSF and IL-1β in their tumors. On the other hand, mice bearing non-metastatic 67NR tumors showed no elevation in neutrophil counts and displayed low expression levels of G-CSF and IL-1β in their tumors. 4T1 tumor-bearing mice but not 67NR tumor-bearing mice exhibited a NET-dependent prothrombotic state. Pharmacological blockade of IL-1 receptor (IL-1R) decreased the primary growth of 4T1 tumors and reduced the systemic levels of myeloperoxidase, cell-free DNA (cfDNA) and G-CSF, without interfering with the neutrophil counts. Most remarkably, the blockade of IL-1R abolished the prothrombotic state observed in 4T1 tumor-bearing mice. Overall, our results demonstrate that IL-1β might be a feasible target to attenuate cancer-associated thrombosis, particularly in cancer types that rely on increased G-CSF production and involvement of NET formation. |
| first_indexed | 2024-12-10T21:20:44Z |
| format | Article |
| id | doaj.art-e4a7c9f09fe940ea9664ad395f747e82 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T21:20:44Z |
| publishDate | 2019-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e4a7c9f09fe940ea9664ad395f747e822022-12-22T01:33:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-09-011010.3389/fimmu.2019.02088435730IL-1β Blockade Attenuates Thrombosis in a Neutrophil Extracellular Trap-Dependent Breast Cancer ModelTainá Gomes0Carolina B. S. Várady1André L. Lourenço2Daniella M. Mizurini3Araci M. R. Rondon4Ana C. Leal5Barbara S. Gonçalves6Dumith Chequer Bou-Habib7Dumith Chequer Bou-Habib8Emiliano Medei9Robson Q. Monteiro10Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilLaboratory on Thymus Research, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, BrazilLaboratory on Thymus Research, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, BrazilNational Institute of Science and Technology on Neuroimmunomodulation, Rio de Janeiro, BrazilCarlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilCancer patients are at increased risk of developing thrombosis, comorbidity that has been associated with increased neutrophil counts and the formation of neutrophil extracellular traps (NETs). Interleukin-1β (IL-1β) modulates the expression of granulocyte colony-stimulating factor (G-CSF), a cytokine that promotes cancer-associated neutrophilia and NET generation. Herein, we combined a murine breast cancer model with a flow-restriction thrombosis model to evaluate whether the IL-1β blockade could interfere with cancer-associated thrombosis. Mice bearing metastatic 4T1 tumors exhibited high neutrophil counts as well as elevated expression of G-CSF and IL-1β in their tumors. On the other hand, mice bearing non-metastatic 67NR tumors showed no elevation in neutrophil counts and displayed low expression levels of G-CSF and IL-1β in their tumors. 4T1 tumor-bearing mice but not 67NR tumor-bearing mice exhibited a NET-dependent prothrombotic state. Pharmacological blockade of IL-1 receptor (IL-1R) decreased the primary growth of 4T1 tumors and reduced the systemic levels of myeloperoxidase, cell-free DNA (cfDNA) and G-CSF, without interfering with the neutrophil counts. Most remarkably, the blockade of IL-1R abolished the prothrombotic state observed in 4T1 tumor-bearing mice. Overall, our results demonstrate that IL-1β might be a feasible target to attenuate cancer-associated thrombosis, particularly in cancer types that rely on increased G-CSF production and involvement of NET formation.https://www.frontiersin.org/article/10.3389/fimmu.2019.02088/fullcancerIL-1βG-CSFneutrophil extracellular trap (NET)thrombosis |
| spellingShingle | Tainá Gomes Carolina B. S. Várady André L. Lourenço Daniella M. Mizurini Araci M. R. Rondon Ana C. Leal Barbara S. Gonçalves Dumith Chequer Bou-Habib Dumith Chequer Bou-Habib Emiliano Medei Robson Q. Monteiro IL-1β Blockade Attenuates Thrombosis in a Neutrophil Extracellular Trap-Dependent Breast Cancer Model Frontiers in Immunology cancer IL-1β G-CSF neutrophil extracellular trap (NET) thrombosis |
| title | IL-1β Blockade Attenuates Thrombosis in a Neutrophil Extracellular Trap-Dependent Breast Cancer Model |
| title_full | IL-1β Blockade Attenuates Thrombosis in a Neutrophil Extracellular Trap-Dependent Breast Cancer Model |
| title_fullStr | IL-1β Blockade Attenuates Thrombosis in a Neutrophil Extracellular Trap-Dependent Breast Cancer Model |
| title_full_unstemmed | IL-1β Blockade Attenuates Thrombosis in a Neutrophil Extracellular Trap-Dependent Breast Cancer Model |
| title_short | IL-1β Blockade Attenuates Thrombosis in a Neutrophil Extracellular Trap-Dependent Breast Cancer Model |
| title_sort | il 1β blockade attenuates thrombosis in a neutrophil extracellular trap dependent breast cancer model |
| topic | cancer IL-1β G-CSF neutrophil extracellular trap (NET) thrombosis |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02088/full |
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