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Local iron homeostasis in the breast ductal carcinoma microenvironment

2016-03-05Journal article Open access
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dc.contributor.authorMarques, O.
dc.contributor.authorPorto, G.
dc.contributor.authorRêma, A.
dc.contributor.authorFaria, F.
dc.contributor.authorCruz Paula, A.
dc.contributor.authorGomez-Lazaro, M.
dc.contributor.authorSilva, P.
dc.contributor.authorMartins-Silva, B.
dc.contributor.authorLopes, C.
dc.date.accessioned2017-05-09T12:58:17Z
dc.date.available2017-05-09T12:58:17Z
dc.date.issued2016-03-05
dc.description.abstractAbstract 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBMC Cancer. (2016)16:187pt_PT
dc.identifier.doi10.1186/s12885-016-2228-ypt_PT
dc.identifier.issn1471-2407
dc.identifier.urihttp://hdl.handle.net/10400.16/2085
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherBioMed Centralpt_PT
dc.relationSFRH/BD/2011/78184pt_PT
dc.relationDEREGULATION OF NOTCH SIGNALING PATHWAY OF BREAST STEM CELLS IN PROLIFERATIVE, PRE-MALIGNANT, AND NEOPLASIA LESIONS OF BREAST
dc.relation.publisherversionhttps://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2228-ypt_PT
dc.subjectBreast cancerpt_PT
dc.subjectFerroportin 1pt_PT
dc.subjectIronpt_PT
dc.subjectStromal inflammatory cellspt_PT
dc.subjectTissue microenvironmentpt_PT
dc.subjectIronpt_PT
dc.subjectLymph Nodespt_PT
dc.subjectReceptors, Transferrinpt_PT
dc.subjectTumor Burdenpt_PT
dc.subjectHomeostasispt_PT
dc.subjectTumor Microenvironmentpt_PT
dc.titleLocal iron homeostasis in the breast ductal carcinoma microenvironmentpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleDEREGULATION OF NOTCH SIGNALING PATHWAY OF BREAST STEM CELLS IN PROLIFERATIVE, PRE-MALIGNANT, AND NEOPLASIA LESIONS OF BREAST
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/FARH/SFRH%2FBD%2F74307%2F2010/PT
oaire.citation.conferencePlaceEnglandpt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage187pt_PT
oaire.citation.titleBMC Cancerpt_PT
oaire.citation.volume16pt_PT
oaire.fundingStreamFARH
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationb75607be-3379-4f71-9b0b-8aead9c2c718
relation.isProjectOfPublication.latestForDiscoveryb75607be-3379-4f71-9b0b-8aead9c2c718

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