Challenging metastatic breast cancer with the natural defensin PvD1

Detalhes bibliográficos
Autor(a) principal: Figueira, Tiago N.
Data de Publicação: 2017
Outros Autores: Oliveira, Filipa D., Almeida, Inês, Mello, Érica O., Gomes, Valdirene M., Castanho, Miguel A. R. B., Gaspar, Diana
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/32530
Resumo: © The Royal Society of Chemistry 2017
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spelling Challenging metastatic breast cancer with the natural defensin PvD1© The Royal Society of Chemistry 2017Metastatic breast cancer is a very serious life threatening condition that poses many challenges for the pharmaceutical development of effective chemotherapeutics. As the therapeutics targeted to the localized masses in breast improve, metastatic lesions in the brain slowly increase in their incidence compromising successful treatment outcomes overall. The blood-brain-barrier (BBB) is one important obstacle for the management of breast cancer brain metastases. New therapeutic approaches are in demand for overcoming the BBB's breaching by breast tumor cells. In this work we demonstrate the potential dual role of a natural antimicrobial plant defensin, PvD1: it interferes with the formation of solid tumors in the breast and concomitantly controls adhesion of breast cancer cells to human brain endothelial cells. We have used a combination of techniques that probe PvD1's effect at the single cell level and reveal that this peptide can effectively damage breast tumor cells, leaving healthy breast and brain cells unaffected. Results suggest that PvD1 quickly internalizes in cancer cells but remains located in the membrane of normal cells with no significant damage to its structure and biomechanical properties. These interactions in turn modulate cell adhesiveness between tumor and BBB cells. PvD1 is a potential template for the design of innovative pharmacological approaches for metastatic breast cancer treatment: the manipulation of the biomechanical properties of tumor cells that ultimately prevent their attachment to the BBB.This work was supported by a grant from Laço (Portugal). The authors thank Fundação para a Ciência e a Tecnologia (FCT I.P., Portugal) for funding—PTDC/BBB-BQB/1693/2014 and LISBOA-01-0145-FEDER-007391, project co-financed by FEDER through POR Lisboa 2020 - Programa Operacional Regional de Lisboa, Portugal 2020, and by Fundação para a Ciência e a Tecnologia, and also acknowledge financial support from the Brazilian agencies CNPq, CAPES, and FAPERJ (E-26/203.090/2016; E-26/202.132/2015). Tiago N. Figueira, Filipa D. Oliveira and Diana Gaspar acknowledge FCT I.P. for fellowships SFRH/ BD/5283/2013, PD/BD/135046/2017 and SFRH/BPD/109010/2015. Marie Skłodowska-Curie Research and Innovation Staff Exchange (RISE) is also acknowledged for funding: call H2020-MSCA-RISE-2014, Grant agreement 644167, 2015–2019. Prof. Teresa R. Pacheco (FMUL) and Prof. Alexandra Brito (FFUL) are acknowledged for providing the human breast cell lines and HBMEC primary culture, respectively.Royal Society of ChemistryRepositório da Universidade de LisboaFigueira, Tiago N.Oliveira, Filipa D.Almeida, InêsMello, Érica O.Gomes, Valdirene M.Castanho, Miguel A. R. B.Gaspar, Diana2018-04-02T11:16:12Z20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/32530engNanoscale, 2017,9, 16887-168992040-336410.1039/c7nr05872ainfo: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:RCAAP2023-07-14T15:22:06ZPortal AgregadorONG
dc.title.none.fl_str_mv Challenging metastatic breast cancer with the natural defensin PvD1
title Challenging metastatic breast cancer with the natural defensin PvD1
spellingShingle Challenging metastatic breast cancer with the natural defensin PvD1
Figueira, Tiago N.
title_short Challenging metastatic breast cancer with the natural defensin PvD1
title_full Challenging metastatic breast cancer with the natural defensin PvD1
title_fullStr Challenging metastatic breast cancer with the natural defensin PvD1
title_full_unstemmed Challenging metastatic breast cancer with the natural defensin PvD1
title_sort Challenging metastatic breast cancer with the natural defensin PvD1
author Figueira, Tiago N.
author_facet Figueira, Tiago N.
Oliveira, Filipa D.
Almeida, Inês
Mello, Érica O.
Gomes, Valdirene M.
Castanho, Miguel A. R. B.
Gaspar, Diana
author_role author
author2 Oliveira, Filipa D.
Almeida, Inês
Mello, Érica O.
Gomes, Valdirene M.
Castanho, Miguel A. R. B.
Gaspar, Diana
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Figueira, Tiago N.
Oliveira, Filipa D.
Almeida, Inês
Mello, Érica O.
Gomes, Valdirene M.
Castanho, Miguel A. R. B.
Gaspar, Diana
description © The Royal Society of Chemistry 2017
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-01-01T00:00:00Z
2018-04-02T11:16:12Z
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/10451/32530
url http://hdl.handle.net/10451/32530
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Nanoscale, 2017,9, 16887-16899
2040-3364
10.1039/c7nr05872a
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 Royal Society of Chemistry
publisher.none.fl_str_mv Royal Society of Chemistry
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
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instacron_str RCAAP
institution RCAAP
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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