Papel do tecido adiposo de indivíduos obesos sobre células tumorais de mama
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UERJ |
Texto Completo: | http://www.bdtd.uerj.br/handle/1/18569 |
Resumo: | Obesity is a multifactorial disease characterized by a meta-inflammation sustained by the adipose tissue (TA). It constitutes a major public health problem because of its impact on public coffers and especially because of its association with several diseases, including cancer. Evidences show that obesity is linked to a worse prognosis and an increased risk of death in women with breast cancer. In order to evaluate the influence of adipose tissue (AT) on tumor cells, we stimulated, in vitro, human mammary adenocarcinoma cells (MCF-7 and MDA-MB-231) with conditioned medium (CM) or extracellular vesicle fraction (MPs) secreted by AT derived from obese or lean individuals, which were obtained during bariatric or plastic surgery, respectively. Our objective was to investigate the effects of secretion from obese AT on breast cancer cells, as well as the mechanisms and signaling pathways behind them. MCF-7 and MDA-MB-231 cells were stimulated for 24 h with 20% (V/V) MC or MPs (20 μg/ml) derived from obese or lean individuals; the cell proliferation assay was evaluated by the MTT method in the presence or absence of the MAPK/ERK pathway inhibitor (PD98059); cell migration was performed by the wound healing method and cell invasion by transwell migration (coated with 1% gelatin), both in the presence or absence of the PI3K/AKT pathway inhibitor (LY294002); ERK and AKT expression (in MCF-7 and MDA-MB-231 cells) and expression of MMP-2 and 9 (in MPs) were evaluated by Western blotting; for the Matrigel tubulogenesis assays, endothelial cells (HMEC-1) were incubated with the culture supernatant from untreated MDA-MB-231 cells or MDA-MB-231 cells previously treated with the CM derived from the obese AT; MMP-9 mRNA expression was evaluated by real-time PCR; the proteolytic activity of MMP-2 and 9 present in the MPs was evaluated by zymography. Our results demonstrated that MC and MPs from obese AT increased the proliferation of MCF-7 cells, without altering it in MDA-MB-231 cells. On the other hand, MC and MPs from obese AT increased the migration and invasiveness of MDA-MB-231 cells. In addition, we observed that both the CM and MPs released by obese AT increased ERK phosphorylation in MCF-7 cells, while only MPs increased the phosphorylation of AKT in MDA-MB-231 cells. The MAPK/ERK inhibitor decreased the proliferation of MCF-7 cells, whereas the PI3K/AKT inhibitor decreased both migration and invasion of MDA-MB-231 cells. Additionally, we observed that the treatment of the HMEC-1 cells with the supernatant from MDA-MB-231 cells previously treated with the CM from the obese AT showed increased tubulogenic capacity. It is important to note that this effect was not observed when HMEC-1 cells were treated with only the CM from obese AT. Interestingly, the MPs released by obese AT were enriched in bioactives MMP-2 and 9, possibly explaining the increase in the invasive capacity of these cells. Taken together, our results indicate that the microenvironment of obese AT influences priority functions for the progression of breast cancer, increasing the malignancy of the tumor cells through the secretion by molecules and MPs from AT with pro-tumor activities. |
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Barja-Fidalgo, Thereza Christinahttp://lattes.cnpq.br/7181616799746888Martins, Mariana Renovatohttp://lattes.cnpq.br/4873004948911165Monteiro, Robson de Queirozhttp://lattes.cnpq.br/0848413770343284Lindoso, Rafael Soareshttp://lattes.cnpq.br/2868007778082108Simão, Tatiana de Almeidahttp://lattes.cnpq.br/4257729756468950http://lattes.cnpq.br/5655549590220706Andrade, Isadora Ramos deisadora.andrade@yahoo.com.br2022-10-31T13:17:57Z2022-06-03ANDRADE, Isadora Ramos de. Papel do tecido adiposo de indivíduos obesos sobre células tumorais de mama. 2018. 93 f. Dissertação (Mestrado em Biociências) – Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2018.http://www.bdtd.uerj.br/handle/1/18569Obesity is a multifactorial disease characterized by a meta-inflammation sustained by the adipose tissue (TA). It constitutes a major public health problem because of its impact on public coffers and especially because of its association with several diseases, including cancer. Evidences show that obesity is linked to a worse prognosis and an increased risk of death in women with breast cancer. In order to evaluate the influence of adipose tissue (AT) on tumor cells, we stimulated, in vitro, human mammary adenocarcinoma cells (MCF-7 and MDA-MB-231) with conditioned medium (CM) or extracellular vesicle fraction (MPs) secreted by AT derived from obese or lean individuals, which were obtained during bariatric or plastic surgery, respectively. Our objective was to investigate the effects of secretion from obese AT on breast cancer cells, as well as the mechanisms and signaling pathways behind them. MCF-7 and MDA-MB-231 cells were stimulated for 24 h with 20% (V/V) MC or MPs (20 μg/ml) derived from obese or lean individuals; the cell proliferation assay was evaluated by the MTT method in the presence or absence of the MAPK/ERK pathway inhibitor (PD98059); cell migration was performed by the wound healing method and cell invasion by transwell migration (coated with 1% gelatin), both in the presence or absence of the PI3K/AKT pathway inhibitor (LY294002); ERK and AKT expression (in MCF-7 and MDA-MB-231 cells) and expression of MMP-2 and 9 (in MPs) were evaluated by Western blotting; for the Matrigel tubulogenesis assays, endothelial cells (HMEC-1) were incubated with the culture supernatant from untreated MDA-MB-231 cells or MDA-MB-231 cells previously treated with the CM derived from the obese AT; MMP-9 mRNA expression was evaluated by real-time PCR; the proteolytic activity of MMP-2 and 9 present in the MPs was evaluated by zymography. Our results demonstrated that MC and MPs from obese AT increased the proliferation of MCF-7 cells, without altering it in MDA-MB-231 cells. On the other hand, MC and MPs from obese AT increased the migration and invasiveness of MDA-MB-231 cells. In addition, we observed that both the CM and MPs released by obese AT increased ERK phosphorylation in MCF-7 cells, while only MPs increased the phosphorylation of AKT in MDA-MB-231 cells. The MAPK/ERK inhibitor decreased the proliferation of MCF-7 cells, whereas the PI3K/AKT inhibitor decreased both migration and invasion of MDA-MB-231 cells. Additionally, we observed that the treatment of the HMEC-1 cells with the supernatant from MDA-MB-231 cells previously treated with the CM from the obese AT showed increased tubulogenic capacity. It is important to note that this effect was not observed when HMEC-1 cells were treated with only the CM from obese AT. Interestingly, the MPs released by obese AT were enriched in bioactives MMP-2 and 9, possibly explaining the increase in the invasive capacity of these cells. Taken together, our results indicate that the microenvironment of obese AT influences priority functions for the progression of breast cancer, increasing the malignancy of the tumor cells through the secretion by molecules and MPs from AT with pro-tumor activities.A obesidade é uma doença multifatorial caracterizada por um quadro de metainflamação sustentado pelo tecido adiposo (TA). A mesma se constitui em um grande problema de saúde pública pelo seu impacto nos cofres públicos e principalmente por sua associação com diversas doenças, incluindo o câncer. Evidências mostram que a obesidade está ligada a um pior prognóstico e um risco aumentado de morte em mulheres com câncer de mama. Com o objetivo de estudar os efeitos da obesidade sobre o desenvolvimento e progressão tumoral, investigamos a influência de fatores secretados pelo TA sobre células de adenocarcinoma mamário humano. Para tanto, as células MCF-7 e MDA-MB-231 foram estimuladas, in vitro, com o meio condicionado (MC) ou com a fração de vesículas extracelulares (MPs) secretados por TAs obtidos, respectivamente, de indivíduos obesos ou eutróficos durante cirurgia bariátrica ou plástica, avaliando-se as alterações induzidas sobre a homeostasia e função dessas células, além dos mecanismos e vias de sinalização envolvidos. Para tanto, as células MCF-7 e MDA-MB-231 foram estimuladas durante 24h com 20% (v/v) de MC ou com MPs (20 μg/ml) derivadas de indivíduos obesos ou eutróficos. O ensaio de proliferação celular foi avaliado pelo método MTT, na presença ou ausência do inibidor da via MAPK/ERK (PD98059); a migração celular foi avaliada através do método de wound healing e a invasão celular por migração através do uso de insertos porosos do tipo transwell (revestido com gelatina 1%), ambos na presença ou ausência do inibidor da via PI3K/AKT (LY294002). A expressão de ERK e AKT nas células MCF-7 e MDA-MB-231 e a expressão de MMP-2 e MMP-9 nas MPs foram analisadas por Western Blotting. A expressão de RNAm para MMP-9 foi avaliada por PCR em tempo real; a atividade proteolítica de MMP-2 e 9 presentes nas MPs foi avaliada por zimografia. Para os ensaios de tubulogênese em Matrigel, as células endoteliais (HMEC-1) foram incubadas com o sobrenadante de células MDA-MB-231 sem tratamento ou previamente tratadas com o MC derivado do TA obeso. Nossos resultados mostraram que em comparação ao TA magro, o MC e as MPs oriundos do TA obeso induziram aumento na proliferação das células MCF-7, sem alterá-la nas células MDA-MB-231. Por outro lado, o MC e as MPs do TA obeso aumentaram a migração e invasividade das células MDA-MB-231. Além disso, observamos que as MPs liberadas pelo TA obeso aumentaram a fosforilação de ERK nas células MCF-7, enquanto aumentaram a fosforilação de AKT nas células MDA-MB-231. O inibidor de MAPK/ERK diminuiu a proliferação das células MCF-7, enquanto o inibidor da PI3K/AKT diminuiu tanto a migração quanto a invasão das células MDA-MB-231. Adicionalmente, observamos que o tratamento das células HMEC-1 com o sobrenadante das células MDA-MB-231 previamente tratadas com o MC do TA obeso apresentaram maior capacidade tubulogênica em comparação ao tratamento do MC do TA magro. Este efeito não foi observado quando as células HMEC-1 foram tratadas diretamente com o MC oriundo do TA obeso. Observamos ainda que as MPs liberadas pelo TA obeso são enriquecidas em MMP-2 e MMP-9 bioativas, corroborando o aumento da capacidade invasiva dessas células no ambiete obeso. Em conjunto, nossos resultados indicam que o microambiente do TA obeso influencia funções celulares prioritárias para a progressão do câncer de mama, aumentando a malignidade das céluals tumorais através da secreção pelo TA de moléculas e de MPs com atividades pró-tumorais.Submitted by Heloísa CB/A (helobdtd@gmail.com) on 2022-10-31T13:17:57Z No. of bitstreams: 1 Dissertação - Isadora Ramos de Andrade - 2018 - Completo.pdf: 2668647 bytes, checksum: 3cd303e3f45562f047836f6a00a3dacb (MD5)Made available in DSpace on 2022-10-31T13:17:57Z (GMT). No. of bitstreams: 1 Dissertação - Isadora Ramos de Andrade - 2018 - Completo.pdf: 2668647 bytes, checksum: 3cd303e3f45562f047836f6a00a3dacb (MD5) Previous issue date: 2022-06-03Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfporUniversidade do Estado do Rio de JaneiroPrograma de Pós-Graduação em BiociênciasUERJBrasilCentro Biomédico::Instituto de Biologia Roberto Alcantara GomesObesityAdipose tissueMicroparticlesBreast cancerObesidadeTecido adiposoMicropartículasCâncer de mamaCIENCIAS BIOLOGICASPapel do tecido adiposo de indivíduos obesos sobre células tumorais de mamaRole of adipose tissue from obese subjects on breast tumor cellsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UERJinstname:Universidade do Estado do Rio de Janeiro (UERJ)instacron:UERJORIGINALDissertação - Isadora Ramos de Andrade - 2018 - Completo.pdfDissertação - Isadora Ramos de Andrade - 2018 - Completo.pdfapplication/pdf2668647http://www.bdtd.uerj.br/bitstream/1/18569/2/Disserta%C3%A7%C3%A3o+-+Isadora+Ramos+de+Andrade+-+2018+-+Completo.pdf3cd303e3f45562f047836f6a00a3dacbMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82123http://www.bdtd.uerj.br/bitstream/1/18569/1/license.txte5502652da718045d7fcd832b79fca29MD511/185692024-02-26 11:25:03.342oai:www.bdtd.uerj.br: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Biblioteca Digital de Teses e Dissertaçõeshttp://www.bdtd.uerj.br/PUBhttps://www.bdtd.uerj.br:8443/oai/requestbdtd.suporte@uerj.bropendoar:29032024-02-26T14:25:03Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ)false |
dc.title.por.fl_str_mv |
Papel do tecido adiposo de indivíduos obesos sobre células tumorais de mama |
dc.title.alternative.eng.fl_str_mv |
Role of adipose tissue from obese subjects on breast tumor cells |
title |
Papel do tecido adiposo de indivíduos obesos sobre células tumorais de mama |
spellingShingle |
Papel do tecido adiposo de indivíduos obesos sobre células tumorais de mama Andrade, Isadora Ramos de Obesity Adipose tissue Microparticles Breast cancer Obesidade Tecido adiposo Micropartículas Câncer de mama CIENCIAS BIOLOGICAS |
title_short |
Papel do tecido adiposo de indivíduos obesos sobre células tumorais de mama |
title_full |
Papel do tecido adiposo de indivíduos obesos sobre células tumorais de mama |
title_fullStr |
Papel do tecido adiposo de indivíduos obesos sobre células tumorais de mama |
title_full_unstemmed |
Papel do tecido adiposo de indivíduos obesos sobre células tumorais de mama |
title_sort |
Papel do tecido adiposo de indivíduos obesos sobre células tumorais de mama |
author |
Andrade, Isadora Ramos de |
author_facet |
Andrade, Isadora Ramos de isadora.andrade@yahoo.com.br |
author_role |
author |
author2 |
isadora.andrade@yahoo.com.br |
author2_role |
author |
dc.contributor.advisor1.fl_str_mv |
Barja-Fidalgo, Thereza Christina |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/7181616799746888 |
dc.contributor.advisor-co1.fl_str_mv |
Martins, Mariana Renovato |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/4873004948911165 |
dc.contributor.referee1.fl_str_mv |
Monteiro, Robson de Queiroz |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/0848413770343284 |
dc.contributor.referee2.fl_str_mv |
Lindoso, Rafael Soares |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/2868007778082108 |
dc.contributor.referee3.fl_str_mv |
Simão, Tatiana de Almeida |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/4257729756468950 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/5655549590220706 |
dc.contributor.author.fl_str_mv |
Andrade, Isadora Ramos de isadora.andrade@yahoo.com.br |
contributor_str_mv |
Barja-Fidalgo, Thereza Christina Martins, Mariana Renovato Monteiro, Robson de Queiroz Lindoso, Rafael Soares Simão, Tatiana de Almeida |
dc.subject.eng.fl_str_mv |
Obesity Adipose tissue Microparticles Breast cancer |
topic |
Obesity Adipose tissue Microparticles Breast cancer Obesidade Tecido adiposo Micropartículas Câncer de mama CIENCIAS BIOLOGICAS |
dc.subject.por.fl_str_mv |
Obesidade Tecido adiposo Micropartículas Câncer de mama |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS |
description |
Obesity is a multifactorial disease characterized by a meta-inflammation sustained by the adipose tissue (TA). It constitutes a major public health problem because of its impact on public coffers and especially because of its association with several diseases, including cancer. Evidences show that obesity is linked to a worse prognosis and an increased risk of death in women with breast cancer. In order to evaluate the influence of adipose tissue (AT) on tumor cells, we stimulated, in vitro, human mammary adenocarcinoma cells (MCF-7 and MDA-MB-231) with conditioned medium (CM) or extracellular vesicle fraction (MPs) secreted by AT derived from obese or lean individuals, which were obtained during bariatric or plastic surgery, respectively. Our objective was to investigate the effects of secretion from obese AT on breast cancer cells, as well as the mechanisms and signaling pathways behind them. MCF-7 and MDA-MB-231 cells were stimulated for 24 h with 20% (V/V) MC or MPs (20 μg/ml) derived from obese or lean individuals; the cell proliferation assay was evaluated by the MTT method in the presence or absence of the MAPK/ERK pathway inhibitor (PD98059); cell migration was performed by the wound healing method and cell invasion by transwell migration (coated with 1% gelatin), both in the presence or absence of the PI3K/AKT pathway inhibitor (LY294002); ERK and AKT expression (in MCF-7 and MDA-MB-231 cells) and expression of MMP-2 and 9 (in MPs) were evaluated by Western blotting; for the Matrigel tubulogenesis assays, endothelial cells (HMEC-1) were incubated with the culture supernatant from untreated MDA-MB-231 cells or MDA-MB-231 cells previously treated with the CM derived from the obese AT; MMP-9 mRNA expression was evaluated by real-time PCR; the proteolytic activity of MMP-2 and 9 present in the MPs was evaluated by zymography. Our results demonstrated that MC and MPs from obese AT increased the proliferation of MCF-7 cells, without altering it in MDA-MB-231 cells. On the other hand, MC and MPs from obese AT increased the migration and invasiveness of MDA-MB-231 cells. In addition, we observed that both the CM and MPs released by obese AT increased ERK phosphorylation in MCF-7 cells, while only MPs increased the phosphorylation of AKT in MDA-MB-231 cells. The MAPK/ERK inhibitor decreased the proliferation of MCF-7 cells, whereas the PI3K/AKT inhibitor decreased both migration and invasion of MDA-MB-231 cells. Additionally, we observed that the treatment of the HMEC-1 cells with the supernatant from MDA-MB-231 cells previously treated with the CM from the obese AT showed increased tubulogenic capacity. It is important to note that this effect was not observed when HMEC-1 cells were treated with only the CM from obese AT. Interestingly, the MPs released by obese AT were enriched in bioactives MMP-2 and 9, possibly explaining the increase in the invasive capacity of these cells. Taken together, our results indicate that the microenvironment of obese AT influences priority functions for the progression of breast cancer, increasing the malignancy of the tumor cells through the secretion by molecules and MPs from AT with pro-tumor activities. |
publishDate |
2022 |
dc.date.accessioned.fl_str_mv |
2022-10-31T13:17:57Z |
dc.date.issued.fl_str_mv |
2022-06-03 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
ANDRADE, Isadora Ramos de. Papel do tecido adiposo de indivíduos obesos sobre células tumorais de mama. 2018. 93 f. Dissertação (Mestrado em Biociências) – Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2018. |
dc.identifier.uri.fl_str_mv |
http://www.bdtd.uerj.br/handle/1/18569 |
identifier_str_mv |
ANDRADE, Isadora Ramos de. Papel do tecido adiposo de indivíduos obesos sobre células tumorais de mama. 2018. 93 f. Dissertação (Mestrado em Biociências) – Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2018. |
url |
http://www.bdtd.uerj.br/handle/1/18569 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade do Estado do Rio de Janeiro |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Biociências |
dc.publisher.initials.fl_str_mv |
UERJ |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Centro Biomédico::Instituto de Biologia Roberto Alcantara Gomes |
publisher.none.fl_str_mv |
Universidade do Estado do Rio de Janeiro |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UERJ instname:Universidade do Estado do Rio de Janeiro (UERJ) instacron:UERJ |
instname_str |
Universidade do Estado do Rio de Janeiro (UERJ) |
instacron_str |
UERJ |
institution |
UERJ |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UERJ |
collection |
Biblioteca Digital de Teses e Dissertações da UERJ |
bitstream.url.fl_str_mv |
http://www.bdtd.uerj.br/bitstream/1/18569/2/Disserta%C3%A7%C3%A3o+-+Isadora+Ramos+de+Andrade+-+2018+-+Completo.pdf http://www.bdtd.uerj.br/bitstream/1/18569/1/license.txt |
bitstream.checksum.fl_str_mv |
3cd303e3f45562f047836f6a00a3dacb e5502652da718045d7fcd832b79fca29 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ) |
repository.mail.fl_str_mv |
bdtd.suporte@uerj.br |
_version_ |
1792352368081240064 |