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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| Veröffentlicht in: | Cancers 2020-06, Vol.12 (6), p.1542 |
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| creator | Martins-Cardoso, Karina Almeida, Vitor H. Bagri, Kayo M. Rossi, Maria Isabel Doria Mermelstein, Claudia S. König, Sandra Monteiro, Robson Q. |
| 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. |
| doi_str_mv | 10.3390/cancers12061542 |
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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.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers12061542</identifier><identifier>PMID: 32545405</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Breast cancer ; Cell activation ; Cell adhesion & migration ; Cytokines ; Cytology ; E-cadherin ; Fibronectin ; Flow cytometry ; Gene expression ; Genomes ; Genotype & phenotype ; Immunofluorescence ; Inflammation ; Leukocyte migration ; Mesenchyme ; Metastases ; Metastasis ; Morphology ; N-Cadherin ; Neutrophils ; Phenotypes ; Polymerase chain reaction ; Proteins ; Ribonucleic acid ; RNA ; Stem cells ; Tumor cells ; Tumors ; Western blotting</subject><ispartof>Cancers, 2020-06, Vol.12 (6), p.1542</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c464t-20fda0649b4033d0e64f3929acfbf8e804047a1381972d82176ea2f9bd9119403</citedby><cites>FETCH-LOGICAL-c464t-20fda0649b4033d0e64f3929acfbf8e804047a1381972d82176ea2f9bd9119403</cites><orcidid>0000-0002-5260-2332 ; 0000-0001-8350-173X ; 0000-0003-3432-8453 ; 0000-0002-8897-8526 ; 0000-0002-2789-7116</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352979/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352979/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids></links><search><creatorcontrib>Martins-Cardoso, Karina</creatorcontrib><creatorcontrib>Almeida, Vitor H.</creatorcontrib><creatorcontrib>Bagri, Kayo M.</creatorcontrib><creatorcontrib>Rossi, Maria Isabel Doria</creatorcontrib><creatorcontrib>Mermelstein, Claudia S.</creatorcontrib><creatorcontrib>König, Sandra</creatorcontrib><creatorcontrib>Monteiro, Robson Q.</creatorcontrib><title>Neutrophil Extracellular Traps (NETs) Promote Pro-Metastatic Phenotype in Human Breast Cancer Cells through Epithelial–Mesenchymal Transition</title><title>Cancers</title><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.</description><subject>Breast cancer</subject><subject>Cell activation</subject><subject>Cell adhesion & migration</subject><subject>Cytokines</subject><subject>Cytology</subject><subject>E-cadherin</subject><subject>Fibronectin</subject><subject>Flow cytometry</subject><subject>Gene expression</subject><subject>Genomes</subject><subject>Genotype & phenotype</subject><subject>Immunofluorescence</subject><subject>Inflammation</subject><subject>Leukocyte migration</subject><subject>Mesenchyme</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Morphology</subject><subject>N-Cadherin</subject><subject>Neutrophils</subject><subject>Phenotypes</subject><subject>Polymerase chain reaction</subject><subject>Proteins</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Stem cells</subject><subject>Tumor cells</subject><subject>Tumors</subject><subject>Western blotting</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdUU1P3DAQjapWBVHOvVrqhR5S_JU4vlRqV1uoBJTD9mx5kwkxcuzUdlD31n_QA_-wv6QOIATMZUaaN-_NmymK9wR_Ykzi41a7FkIkFNek4vRVsU-xoGVdS_76Sb1XHMZ4jXMwRkQt3hZ7jFa84rjaL_5ewJyCnwZj0fp3CroFa2erA9oEPUV0dLHexI_oMvjRJ1hyeQ5Jx6STadHlAM6n3QTIOHQ6j9qhrwFyF63udkOrzBZRGoKfrwa0nkwawBpt__25PYcIrh12o7aLlosmGe_eFW96bSMcPuSD4ue39WZ1Wp79OPm--nJWtrzmqaS47zSuudzy7KrDUPOeSSp122_7BhrMMReasIZIQbuGZt-gaS-3nSRE5pmD4vM97zRvR-hacNm7VVMwow475bVRzzvODOrK3yjBKiqFzARHDwTB_5ohJjWauBxPO_BzVJQTzgkV9aL14QX02s_BZXsLiolKSNpk1PE9qg0-xgD94zIEq-Xf6sW_2X9IZqDG</recordid><startdate>20200611</startdate><enddate>20200611</enddate><creator>Martins-Cardoso, Karina</creator><creator>Almeida, Vitor H.</creator><creator>Bagri, Kayo M.</creator><creator>Rossi, Maria Isabel Doria</creator><creator>Mermelstein, Claudia S.</creator><creator>König, Sandra</creator><creator>Monteiro, Robson Q.</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5260-2332</orcidid><orcidid>https://orcid.org/0000-0001-8350-173X</orcidid><orcidid>https://orcid.org/0000-0003-3432-8453</orcidid><orcidid>https://orcid.org/0000-0002-8897-8526</orcidid><orcidid>https://orcid.org/0000-0002-2789-7116</orcidid></search><sort><creationdate>20200611</creationdate><title>Neutrophil Extracellular Traps (NETs) Promote Pro-Metastatic Phenotype in Human Breast Cancer Cells through Epithelial–Mesenchymal Transition</title><author>Martins-Cardoso, Karina ; 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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.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>32545405</pmid><doi>10.3390/cancers12061542</doi><orcidid>https://orcid.org/0000-0002-5260-2332</orcidid><orcidid>https://orcid.org/0000-0001-8350-173X</orcidid><orcidid>https://orcid.org/0000-0003-3432-8453</orcidid><orcidid>https://orcid.org/0000-0002-8897-8526</orcidid><orcidid>https://orcid.org/0000-0002-2789-7116</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Breast cancer Cell activation Cell adhesion & migration Cytokines Cytology E-cadherin Fibronectin Flow cytometry Gene expression Genomes Genotype & phenotype Immunofluorescence Inflammation Leukocyte migration Mesenchyme Metastases Metastasis Morphology N-Cadherin Neutrophils Phenotypes Polymerase chain reaction Proteins Ribonucleic acid RNA Stem cells Tumor cells Tumors Western blotting |
| title | Neutrophil Extracellular Traps (NETs) Promote Pro-Metastatic Phenotype in Human Breast Cancer Cells through Epithelial–Mesenchymal Transition |
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