Neutrophil Extracellular Traps (NETs) Promote Pro-Metastatic Phenotype in Human Breast Cancer Cells through Epithelial–Mesenchymal Transition
Neutrophil extracellular traps (NETs) have been associated with several steps of tumor progression, including primary growth and metastasis. One of the key features for the acquisition of the metastatic ability is the epithelial–mesenchymal transition (EMT), a complex cellular program. In this study...
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| Format: | Article |
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MDPI AG
2020-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/6/1542 |
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| author | Karina Martins-Cardoso Vitor H. Almeida Kayo M. Bagri Maria Isabel Doria Rossi Claudia S. Mermelstein Sandra König Robson Q. Monteiro |
| author_facet | Karina Martins-Cardoso Vitor H. Almeida Kayo M. Bagri Maria Isabel Doria Rossi Claudia S. Mermelstein Sandra König Robson Q. Monteiro |
| author_sort | Karina Martins-Cardoso |
| collection | DOAJ |
| description | Neutrophil extracellular traps (NETs) have been associated with several steps of tumor progression, including primary growth and metastasis. One of the key features for the acquisition of the metastatic ability is the epithelial–mesenchymal transition (EMT), a complex cellular program. In this study, we evaluated the ability of isolated NETs in modulating the pro-metastatic phenotype of human breast cancer cells. Tumor cells were treated with isolated NETs and then samples were generated for cell migration, quantitative RT-PCR, western blotting, immunofluorescence, and flow cytometry assays. RNA-seq data from The Cancer Genome Atlas (TCGA) database were assessed. NETs changed the typical epithelial morphology of MCF7 cells into a mesenchymal phenotype, a process that was accompanied by enhanced migratory properties. Additional EMT traits were observed: increased expression of N-cadherin and fibronectin, while the E-cadherin expression was repressed. Notably, NETs positively regulated the gene expression of several factors linked to the pro-inflammatory and pro-metastatic properties. Analyses of TCGA data showed that samples from breast cancer patients exhibit a significant correlation between pro-tumoral and neutrophil signature gene expression, including several EMT and pro-metastatic factors. Therefore, NETs drive pro-metastatic phenotype in human breast cancer cells through the activation of the EMT program. |
| first_indexed | 2024-03-10T19:14:07Z |
| format | Article |
| id | doaj.art-8047e1dea6d5400cbd910d3966930226 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T19:14:07Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-8047e1dea6d5400cbd910d39669302262023-11-20T03:34:05ZengMDPI AGCancers2072-66942020-06-01126154210.3390/cancers12061542Neutrophil Extracellular Traps (NETs) Promote Pro-Metastatic Phenotype in Human Breast Cancer Cells through Epithelial–Mesenchymal TransitionKarina Martins-Cardoso0Vitor H. Almeida1Kayo M. Bagri2Maria Isabel Doria Rossi3Claudia S. Mermelstein4Sandra König5Robson Q. Monteiro6Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941 590, BrazilInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941 590, BrazilInstitute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941 590, BrazilInstitute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941 590, BrazilInstitute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941 590, BrazilInstitute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941 590, BrazilInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941 590, BrazilNeutrophil extracellular traps (NETs) have been associated with several steps of tumor progression, including primary growth and metastasis. One of the key features for the acquisition of the metastatic ability is the epithelial–mesenchymal transition (EMT), a complex cellular program. In this study, we evaluated the ability of isolated NETs in modulating the pro-metastatic phenotype of human breast cancer cells. Tumor cells were treated with isolated NETs and then samples were generated for cell migration, quantitative RT-PCR, western blotting, immunofluorescence, and flow cytometry assays. RNA-seq data from The Cancer Genome Atlas (TCGA) database were assessed. NETs changed the typical epithelial morphology of MCF7 cells into a mesenchymal phenotype, a process that was accompanied by enhanced migratory properties. Additional EMT traits were observed: increased expression of N-cadherin and fibronectin, while the E-cadherin expression was repressed. Notably, NETs positively regulated the gene expression of several factors linked to the pro-inflammatory and pro-metastatic properties. Analyses of TCGA data showed that samples from breast cancer patients exhibit a significant correlation between pro-tumoral and neutrophil signature gene expression, including several EMT and pro-metastatic factors. Therefore, NETs drive pro-metastatic phenotype in human breast cancer cells through the activation of the EMT program.https://www.mdpi.com/2072-6694/12/6/1542epithelial–mesenchymal transitionneutrophil extracellular trapsbreast cancermetastasis |
| spellingShingle | Karina Martins-Cardoso Vitor H. Almeida Kayo M. Bagri Maria Isabel Doria Rossi Claudia S. Mermelstein Sandra König Robson Q. Monteiro Neutrophil Extracellular Traps (NETs) Promote Pro-Metastatic Phenotype in Human Breast Cancer Cells through Epithelial–Mesenchymal Transition Cancers epithelial–mesenchymal transition neutrophil extracellular traps breast cancer metastasis |
| title | Neutrophil Extracellular Traps (NETs) Promote Pro-Metastatic Phenotype in Human Breast Cancer Cells through Epithelial–Mesenchymal Transition |
| title_full | Neutrophil Extracellular Traps (NETs) Promote Pro-Metastatic Phenotype in Human Breast Cancer Cells through Epithelial–Mesenchymal Transition |
| title_fullStr | Neutrophil Extracellular Traps (NETs) Promote Pro-Metastatic Phenotype in Human Breast Cancer Cells through Epithelial–Mesenchymal Transition |
| title_full_unstemmed | Neutrophil Extracellular Traps (NETs) Promote Pro-Metastatic Phenotype in Human Breast Cancer Cells through Epithelial–Mesenchymal Transition |
| title_short | Neutrophil Extracellular Traps (NETs) Promote Pro-Metastatic Phenotype in Human Breast Cancer Cells through Epithelial–Mesenchymal Transition |
| title_sort | neutrophil extracellular traps nets promote pro metastatic phenotype in human breast cancer cells through epithelial mesenchymal transition |
| topic | epithelial–mesenchymal transition neutrophil extracellular traps breast cancer metastasis |
| url | https://www.mdpi.com/2072-6694/12/6/1542 |
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