Bisphenol A disruption promotes mammary tumor microenvironment via phenotypic cell polarization and inflammatory response
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1002/cbin.12007 http://hdl.handle.net/11449/249786 |
Resumo: | Inflammation in the established tumor microenvironment (TME) is often associated with a poor prognosis of breast cancer. Bisphenol A (BPA) is an endocrine-disrupting chemical that acts as inflammatory promoter and tumoral facilitator in mammary tissue. Previous studies demonstrated the onset of mammary carcinogenesis at aging when BPA exposure occurred in windows of development/susceptibility. We aim to investigate the inflammatory repercussions of BPA in TME in mammary gland (MG) during neoplastic development in aging. Female Mongolian gerbils were exposed to low (50 µg/kg) or high BPA (5000 µg/kg) doses during pregnancy and lactation. They were euthanized at 18 months of age (aging) and the MG were collected for inflammatory markers and histopathological analysis. Contrarily to control MG, BPA induced carcinogenic development mediated by COX-2 and p-STAT3 expression. BPA was also able to promote macrophage and mast cell (MC) polarization in tumoral phenotype, evidenced by pathways for recruitment and activation of these inflammatory cells and tissue invasiveness triggered by tumor necrosis factor-alpha and transforming growth factor-beta 1 (TGF-β1). Increase of tumor-associated macrophages, M1 (CD68 + iNOS+) and M2 (CD163+) expressing pro-tumoral mediators and metalloproteases was observed; this aspect greatly contributed to stromal remodeling and invasion of neoplastic cells. In addition, the MC population drastically increased in BPA-exposed MG. Tryptase-positive MCs increased in disrupted MG and expressed TGF-β1, contributing to EMT process during carcinogenesis mediated by BPA. BPA exposure interfered in inflammatory response by releasing and enhancing the expression of mediators that contribute to tumor growth and recruitment of inflammatory cells that promote a malignant profile. |
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Bisphenol A disruption promotes mammary tumor microenvironment via phenotypic cell polarization and inflammatory responsebisphenol Amast cellsTGF-β1TNF-αtumor-associated macrophagesInflammation in the established tumor microenvironment (TME) is often associated with a poor prognosis of breast cancer. Bisphenol A (BPA) is an endocrine-disrupting chemical that acts as inflammatory promoter and tumoral facilitator in mammary tissue. Previous studies demonstrated the onset of mammary carcinogenesis at aging when BPA exposure occurred in windows of development/susceptibility. We aim to investigate the inflammatory repercussions of BPA in TME in mammary gland (MG) during neoplastic development in aging. Female Mongolian gerbils were exposed to low (50 µg/kg) or high BPA (5000 µg/kg) doses during pregnancy and lactation. They were euthanized at 18 months of age (aging) and the MG were collected for inflammatory markers and histopathological analysis. Contrarily to control MG, BPA induced carcinogenic development mediated by COX-2 and p-STAT3 expression. BPA was also able to promote macrophage and mast cell (MC) polarization in tumoral phenotype, evidenced by pathways for recruitment and activation of these inflammatory cells and tissue invasiveness triggered by tumor necrosis factor-alpha and transforming growth factor-beta 1 (TGF-β1). Increase of tumor-associated macrophages, M1 (CD68 + iNOS+) and M2 (CD163+) expressing pro-tumoral mediators and metalloproteases was observed; this aspect greatly contributed to stromal remodeling and invasion of neoplastic cells. In addition, the MC population drastically increased in BPA-exposed MG. Tryptase-positive MCs increased in disrupted MG and expressed TGF-β1, contributing to EMT process during carcinogenesis mediated by BPA. BPA exposure interfered in inflammatory response by releasing and enhancing the expression of mediators that contribute to tumor growth and recruitment of inflammatory cells that promote a malignant profile.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Department of Biological Sciences Institute of Biosciences Humanities and Exact Sciences São Paulo State University (UNESP), São PauloDepartment of Morphology and Genetics Paulista School of Medicine Federal University of São Paulo (UNIFESP), São PauloLaboratory of Genomic Studies São Paulo State University, São PauloDepartment of Basics Sciences University Center Padre Albino (UNIFIPA), São PauloDepartment of Histology Embryology and Cell Biology Institute of Biological Sciences (ICB III) Federal University of Goiás (UFG), GoiásDepartment of Biological Sciences Institute of Biosciences Humanities and Exact Sciences São Paulo State University (UNESP), São PauloLaboratory of Genomic Studies São Paulo State University, São PauloFAPESP: 18/23383-6FAPESP: 20/00160-1FAPESP: 20/01240-9CNPq: 302938/2020-6Universidade Estadual Paulista (UNESP)Universidade de São Paulo (USP)University Center Padre Albino (UNIFIPA)Universidade Federal de Goiás (UFG)Ruiz, Thalles F. R. [UNESP]Colleta, Simone J. [UNESP]dos Santos, Diego D. [UNESP]Castro, Nayara F. C. [UNESP]Cabral, Ágata S. [UNESP]Calmon, Marilia F. [UNESP]Rahal, Paula [UNESP]Gil, Cristiane D. [UNESP]Girol, Ana PaulaVilamaior, Patricia S. L. [UNESP]Leonel, Ellen C. R.Taboga, Sebastião R. [UNESP]2023-07-29T16:09:11Z2023-07-29T16:09:11Z2023-06-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1136-1146http://dx.doi.org/10.1002/cbin.12007Cell Biology International, v. 47, n. 6, p. 1136-1146, 2023.1095-83551065-6995http://hdl.handle.net/11449/24978610.1002/cbin.120072-s2.0-85150655125Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengCell Biology Internationalinfo:eu-repo/semantics/openAccess2023-07-29T16:09:11Zoai:repositorio.unesp.br:11449/249786Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T22:34:23.328206Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Bisphenol A disruption promotes mammary tumor microenvironment via phenotypic cell polarization and inflammatory response |
title |
Bisphenol A disruption promotes mammary tumor microenvironment via phenotypic cell polarization and inflammatory response |
spellingShingle |
Bisphenol A disruption promotes mammary tumor microenvironment via phenotypic cell polarization and inflammatory response Ruiz, Thalles F. R. [UNESP] bisphenol A mast cells TGF-β1 TNF-α tumor-associated macrophages |
title_short |
Bisphenol A disruption promotes mammary tumor microenvironment via phenotypic cell polarization and inflammatory response |
title_full |
Bisphenol A disruption promotes mammary tumor microenvironment via phenotypic cell polarization and inflammatory response |
title_fullStr |
Bisphenol A disruption promotes mammary tumor microenvironment via phenotypic cell polarization and inflammatory response |
title_full_unstemmed |
Bisphenol A disruption promotes mammary tumor microenvironment via phenotypic cell polarization and inflammatory response |
title_sort |
Bisphenol A disruption promotes mammary tumor microenvironment via phenotypic cell polarization and inflammatory response |
author |
Ruiz, Thalles F. R. [UNESP] |
author_facet |
Ruiz, Thalles F. R. [UNESP] Colleta, Simone J. [UNESP] dos Santos, Diego D. [UNESP] Castro, Nayara F. C. [UNESP] Cabral, Ágata S. [UNESP] Calmon, Marilia F. [UNESP] Rahal, Paula [UNESP] Gil, Cristiane D. [UNESP] Girol, Ana Paula Vilamaior, Patricia S. L. [UNESP] Leonel, Ellen C. R. Taboga, Sebastião R. [UNESP] |
author_role |
author |
author2 |
Colleta, Simone J. [UNESP] dos Santos, Diego D. [UNESP] Castro, Nayara F. C. [UNESP] Cabral, Ágata S. [UNESP] Calmon, Marilia F. [UNESP] Rahal, Paula [UNESP] Gil, Cristiane D. [UNESP] Girol, Ana Paula Vilamaior, Patricia S. L. [UNESP] Leonel, Ellen C. R. Taboga, Sebastião R. [UNESP] |
author2_role |
author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (UNESP) Universidade de São Paulo (USP) University Center Padre Albino (UNIFIPA) Universidade Federal de Goiás (UFG) |
dc.contributor.author.fl_str_mv |
Ruiz, Thalles F. R. [UNESP] Colleta, Simone J. [UNESP] dos Santos, Diego D. [UNESP] Castro, Nayara F. C. [UNESP] Cabral, Ágata S. [UNESP] Calmon, Marilia F. [UNESP] Rahal, Paula [UNESP] Gil, Cristiane D. [UNESP] Girol, Ana Paula Vilamaior, Patricia S. L. [UNESP] Leonel, Ellen C. R. Taboga, Sebastião R. [UNESP] |
dc.subject.por.fl_str_mv |
bisphenol A mast cells TGF-β1 TNF-α tumor-associated macrophages |
topic |
bisphenol A mast cells TGF-β1 TNF-α tumor-associated macrophages |
description |
Inflammation in the established tumor microenvironment (TME) is often associated with a poor prognosis of breast cancer. Bisphenol A (BPA) is an endocrine-disrupting chemical that acts as inflammatory promoter and tumoral facilitator in mammary tissue. Previous studies demonstrated the onset of mammary carcinogenesis at aging when BPA exposure occurred in windows of development/susceptibility. We aim to investigate the inflammatory repercussions of BPA in TME in mammary gland (MG) during neoplastic development in aging. Female Mongolian gerbils were exposed to low (50 µg/kg) or high BPA (5000 µg/kg) doses during pregnancy and lactation. They were euthanized at 18 months of age (aging) and the MG were collected for inflammatory markers and histopathological analysis. Contrarily to control MG, BPA induced carcinogenic development mediated by COX-2 and p-STAT3 expression. BPA was also able to promote macrophage and mast cell (MC) polarization in tumoral phenotype, evidenced by pathways for recruitment and activation of these inflammatory cells and tissue invasiveness triggered by tumor necrosis factor-alpha and transforming growth factor-beta 1 (TGF-β1). Increase of tumor-associated macrophages, M1 (CD68 + iNOS+) and M2 (CD163+) expressing pro-tumoral mediators and metalloproteases was observed; this aspect greatly contributed to stromal remodeling and invasion of neoplastic cells. In addition, the MC population drastically increased in BPA-exposed MG. Tryptase-positive MCs increased in disrupted MG and expressed TGF-β1, contributing to EMT process during carcinogenesis mediated by BPA. BPA exposure interfered in inflammatory response by releasing and enhancing the expression of mediators that contribute to tumor growth and recruitment of inflammatory cells that promote a malignant profile. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-07-29T16:09:11Z 2023-07-29T16:09:11Z 2023-06-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1002/cbin.12007 Cell Biology International, v. 47, n. 6, p. 1136-1146, 2023. 1095-8355 1065-6995 http://hdl.handle.net/11449/249786 10.1002/cbin.12007 2-s2.0-85150655125 |
url |
http://dx.doi.org/10.1002/cbin.12007 http://hdl.handle.net/11449/249786 |
identifier_str_mv |
Cell Biology International, v. 47, n. 6, p. 1136-1146, 2023. 1095-8355 1065-6995 10.1002/cbin.12007 2-s2.0-85150655125 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Cell Biology International |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1136-1146 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1808129438955601920 |