Repository logo
 
Publication

Challenging metastatic breast cancer with the natural defensin PvD1

2017Journal article Open access
Simple item page
dc.contributor.authorFigueira, Tiago N.
dc.contributor.authorOliveira, Filipa D.
dc.contributor.authorAlmeida, Inês
dc.contributor.authorMello, Érica O.
dc.contributor.authorGomes, Valdirene M.
dc.contributor.authorCastanho, Miguel A. R. B.
dc.contributor.authorGaspar, Diana
dc.date.accessioned2018-04-02T11:16:12Z
dc.date.available2018-04-02T11:16:12Z
dc.date.issued2017
dc.description© The Royal Society of Chemistry 2017pt_PT
dc.description.abstractMetastatic 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.pt_PT
dc.description.sponsorshipThis 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNanoscale, 2017,9, 16887-16899pt_PT
dc.identifier.doi10.1039/c7nr05872apt_PT
dc.identifier.issn2040-3364
dc.identifier.urihttp://hdl.handle.net/10451/32530
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherRoyal Society of Chemistrypt_PT
dc.relationLISBOA-01-0145-FEDER-007391pt_PT
dc.relationCell-cell communication in metastatic breast cancer: a control point that can lead to breast cancer treatment
dc.relationExosomes as drug delivery systems in metastatic breast cancer
dc.relationCell-cell direct/indirect communication in metastatic breast cancer as a control point in oncotherapy
dc.relation.publisherversionhttp://pubs.rsc.org/en/Journals/JournalIssues/NR#!recentarticles&advpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleChallenging metastatic breast cancer with the natural defensin PvD1pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCell-cell communication in metastatic breast cancer: a control point that can lead to breast cancer treatment
oaire.awardTitleExosomes as drug delivery systems in metastatic breast cancer
oaire.awardTitleCell-cell direct/indirect communication in metastatic breast cancer as a control point in oncotherapy
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBBB-BQB%2F1693%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F135046%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F109010%2F2015/PT
oaire.citation.endPage16899pt_PT
oaire.citation.issue43pt_PT
oaire.citation.startPage16887pt_PT
oaire.citation.titleNanoscalept_PT
oaire.citation.volume9pt_PT
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication1d62ccb1-a760-46c2-86e0-e3e40d41a318
relation.isProjectOfPublicationf5fbfaa0-4654-4e9e-8d71-7bf0ed5539d5
relation.isProjectOfPublication0ec23e32-e1a5-4681-9cb6-491aae58a6de
relation.isProjectOfPublication.latestForDiscoveryf5fbfaa0-4654-4e9e-8d71-7bf0ed5539d5

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Nanoscale_PvD1.pdf
Size:
3.43 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.2 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

IMM - Artigos em Revistas Internacionais