Local iron homeostasis in the breast ductal carcinoma microenvironment
Autor(a) principal: | |
---|---|
Data de Publicação: | 2016 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.16/2085 |
Resumo: | Abstract BACKGROUND: While the deregulation of iron homeostasis in breast epithelial cells is acknowledged, iron-related alterations in stromal inflammatory cells from the tumor microenvironment have not been explored. METHODS: Immunohistochemistry for hepcidin, ferroportin 1 (FPN1), transferrin receptor 1 (TFR1) and ferritin (FT) was performed in primary breast tissues and axillary lymph nodes in order to dissect the iron-profiles of epithelial cells, lymphocytes and macrophages. Furthermore, breast carcinoma core biopsies frozen in optimum cutting temperature (OCT) compound were subjected to imaging flow cytometry to confirm FPN1 expression in the cell types previously evaluated and determine its cellular localization. RESULTS: We confirm previous results by showing that breast cancer epithelial cells present an 'iron-utilization phenotype' with an increased expression of hepcidin and TFR1, and decreased expression of FT. On the other hand, lymphocytes and macrophages infiltrating primary tumors and from metastized lymph nodes display an 'iron-donor' phenotype, with increased expression of FPN1 and FT, concomitant with an activation profile reflected by a higher expression of TFR1 and hepcidin. A higher percentage of breast carcinomas, compared to control mastectomy samples, present iron accumulation in stromal inflammatory cells, suggesting that these cells may constitute an effective tissue iron reservoir. Additionally, not only the deregulated expression of iron-related proteins in epithelial cells, but also on lymphocytes and macrophages, are associated with clinicopathological markers of breast cancer poor prognosis, such as negative hormone receptor status and tumor size. CONCLUSIONS: The present results reinforce the importance of analyzing the tumor microenvironment in breast cancer, extending the contribution of immune cells to local iron homeostasis in the tumor microenvironment context. |
id |
RCAP_55b91490dc0c9ba28407da8da903b5ae |
---|---|
oai_identifier_str |
oai:repositorio.chporto.pt:10400.16/2085 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
|
spelling |
Local iron homeostasis in the breast ductal carcinoma microenvironmentBreast cancerFerroportin 1IronStromal inflammatory cellsTissue microenvironmentIronLymph NodesReceptors, TransferrinTumor BurdenHomeostasisTumor MicroenvironmentAbstract BACKGROUND: While the deregulation of iron homeostasis in breast epithelial cells is acknowledged, iron-related alterations in stromal inflammatory cells from the tumor microenvironment have not been explored. METHODS: Immunohistochemistry for hepcidin, ferroportin 1 (FPN1), transferrin receptor 1 (TFR1) and ferritin (FT) was performed in primary breast tissues and axillary lymph nodes in order to dissect the iron-profiles of epithelial cells, lymphocytes and macrophages. Furthermore, breast carcinoma core biopsies frozen in optimum cutting temperature (OCT) compound were subjected to imaging flow cytometry to confirm FPN1 expression in the cell types previously evaluated and determine its cellular localization. RESULTS: We confirm previous results by showing that breast cancer epithelial cells present an 'iron-utilization phenotype' with an increased expression of hepcidin and TFR1, and decreased expression of FT. On the other hand, lymphocytes and macrophages infiltrating primary tumors and from metastized lymph nodes display an 'iron-donor' phenotype, with increased expression of FPN1 and FT, concomitant with an activation profile reflected by a higher expression of TFR1 and hepcidin. A higher percentage of breast carcinomas, compared to control mastectomy samples, present iron accumulation in stromal inflammatory cells, suggesting that these cells may constitute an effective tissue iron reservoir. Additionally, not only the deregulated expression of iron-related proteins in epithelial cells, but also on lymphocytes and macrophages, are associated with clinicopathological markers of breast cancer poor prognosis, such as negative hormone receptor status and tumor size. CONCLUSIONS: The present results reinforce the importance of analyzing the tumor microenvironment in breast cancer, extending the contribution of immune cells to local iron homeostasis in the tumor microenvironment context.BioMed CentralRepositório Científico do Centro Hospitalar do PortoMarques, O.Porto, G.Rêma, A.Faria, F.Cruz Paula, A.Gomez-Lazaro, M.Silva, P.Martins-Silva, B.Lopes, C.2017-05-09T12:58:17Z2016-03-05T00:00:00Z2016-03-05T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.16/2085engBMC Cancer. (2016)16:1871471-240710.1186/s12885-016-2228-yinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-09-05T12:40:38ZPortal AgregadorONG |
dc.title.none.fl_str_mv |
Local iron homeostasis in the breast ductal carcinoma microenvironment |
title |
Local iron homeostasis in the breast ductal carcinoma microenvironment |
spellingShingle |
Local iron homeostasis in the breast ductal carcinoma microenvironment Marques, O. Breast cancer Ferroportin 1 Iron Stromal inflammatory cells Tissue microenvironment Iron Lymph Nodes Receptors, Transferrin Tumor Burden Homeostasis Tumor Microenvironment |
title_short |
Local iron homeostasis in the breast ductal carcinoma microenvironment |
title_full |
Local iron homeostasis in the breast ductal carcinoma microenvironment |
title_fullStr |
Local iron homeostasis in the breast ductal carcinoma microenvironment |
title_full_unstemmed |
Local iron homeostasis in the breast ductal carcinoma microenvironment |
title_sort |
Local iron homeostasis in the breast ductal carcinoma microenvironment |
author |
Marques, O. |
author_facet |
Marques, O. Porto, G. Rêma, A. Faria, F. Cruz Paula, A. Gomez-Lazaro, M. Silva, P. Martins-Silva, B. Lopes, C. |
author_role |
author |
author2 |
Porto, G. Rêma, A. Faria, F. Cruz Paula, A. Gomez-Lazaro, M. Silva, P. Martins-Silva, B. Lopes, C. |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Centro Hospitalar do Porto |
dc.contributor.author.fl_str_mv |
Marques, O. Porto, G. Rêma, A. Faria, F. Cruz Paula, A. Gomez-Lazaro, M. Silva, P. Martins-Silva, B. Lopes, C. |
dc.subject.por.fl_str_mv |
Breast cancer Ferroportin 1 Iron Stromal inflammatory cells Tissue microenvironment Iron Lymph Nodes Receptors, Transferrin Tumor Burden Homeostasis Tumor Microenvironment |
topic |
Breast cancer Ferroportin 1 Iron Stromal inflammatory cells Tissue microenvironment Iron Lymph Nodes Receptors, Transferrin Tumor Burden Homeostasis Tumor Microenvironment |
description |
Abstract BACKGROUND: While the deregulation of iron homeostasis in breast epithelial cells is acknowledged, iron-related alterations in stromal inflammatory cells from the tumor microenvironment have not been explored. METHODS: Immunohistochemistry for hepcidin, ferroportin 1 (FPN1), transferrin receptor 1 (TFR1) and ferritin (FT) was performed in primary breast tissues and axillary lymph nodes in order to dissect the iron-profiles of epithelial cells, lymphocytes and macrophages. Furthermore, breast carcinoma core biopsies frozen in optimum cutting temperature (OCT) compound were subjected to imaging flow cytometry to confirm FPN1 expression in the cell types previously evaluated and determine its cellular localization. RESULTS: We confirm previous results by showing that breast cancer epithelial cells present an 'iron-utilization phenotype' with an increased expression of hepcidin and TFR1, and decreased expression of FT. On the other hand, lymphocytes and macrophages infiltrating primary tumors and from metastized lymph nodes display an 'iron-donor' phenotype, with increased expression of FPN1 and FT, concomitant with an activation profile reflected by a higher expression of TFR1 and hepcidin. A higher percentage of breast carcinomas, compared to control mastectomy samples, present iron accumulation in stromal inflammatory cells, suggesting that these cells may constitute an effective tissue iron reservoir. Additionally, not only the deregulated expression of iron-related proteins in epithelial cells, but also on lymphocytes and macrophages, are associated with clinicopathological markers of breast cancer poor prognosis, such as negative hormone receptor status and tumor size. CONCLUSIONS: The present results reinforce the importance of analyzing the tumor microenvironment in breast cancer, extending the contribution of immune cells to local iron homeostasis in the tumor microenvironment context. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-03-05T00:00:00Z 2016-03-05T00:00:00Z 2017-05-09T12:58:17Z |
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://hdl.handle.net/10400.16/2085 |
url |
http://hdl.handle.net/10400.16/2085 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
BMC Cancer. (2016)16:187 1471-2407 10.1186/s12885-016-2228-y |
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 |
BioMed Central |
publisher.none.fl_str_mv |
BioMed Central |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
|
repository.mail.fl_str_mv |
|
_version_ |
1777301181914152960 |