The antimetastatic breast cancer activity of the viral protein-derived peptide vCPP2319 as revealed by cellular biomechanics

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  • dc.contributor.author Oliveira, Filipa D.
  • dc.contributor.author Cavaco, Marco
  • dc.contributor.author Figueira, Tiago N.
  • dc.contributor.author Valle, Javier
  • dc.contributor.author Neves, Vera
  • dc.contributor.author Andreu Martínez, David
  • dc.contributor.author Gaspar, Diana
  • dc.contributor.author Castanho, Miguel A.R.B.
  • dc.date.accessioned 2021-12-14T06:55:04Z
  • dc.date.available 2021-12-14T06:55:04Z
  • dc.date.issued 2022
  • dc.description.abstract The incidence of metastatic breast cancer (MBC) is increasing and the therapeutic arsenal available to fight it is insufficient. Brain metastases, in particular, represent a major challenge for chemotherapy as the impermeable nature of the blood-brain barrier (BBB) prevents most drugs from targeting cells in the brain. For their ability to transpose biological membranes and transport a broad spectrum of bioactive cargoes, cell-penetrating peptides (CPPs) have been hailed as ideal candidates to deliver drugs across biological barriers. A more ambitious approach is to have the CPP as a drug itself, capable of both killing cancer cells and interacting with the blood/brain interface, therefore blocking the onset of brain metastases. vCPP2319, a viral protein-derived CPP, has both properties as it: (a) is selective toward human breast cancer cells (MDA-MB-231) and increases cell stiffness compared to breast epithelial cells (MCF 10A) hindering the progression of metastases; and (b) adsorbs at the surface of human brain endothelial cells potentially counteracting metastatic cells from reaching the brain. Overall, the results reveal the selective anticancer activity of the peptide vCPP2319, which is also able to reside at the blood-brain interface, therefore counteracting brain penetration by metastatic cancer cells.
  • dc.description.sponsorship FDO, MC, and DG acknowledge FCT I.P. for fellowships PD/BD/135046/2017, PD/BD/128281/2017, and SFRH/ BPD/73500/2010. FCT I.P. is also acknowledged for funding (Projects PTDC/BIA-BQM/5027/2020 and PTDC/BBB-NAN/1578/2014). Marie Skłodowska-Curie Research and Innovation Staff Exchange (RISE) is also acknowledged for funding: call H2020-MSCA-RISE-2014, grant agreement 644167, 2015–2019. Work at UPF was supported by grant AGL2017-84097-C2-2-R and the “María de Maeztu” Program for Units of Excellence in R&D (MDM-2014-0370) from the Spanish Ministry of Economy and Competitiveness (MINECO).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Oliveira FD, Cavaco M, Figueira TN, Valle J, Neves V, Andreu D, Gaspar D, Castanho MARB. The antimetastatic breast cancer activity of the viral protein-derived peptide vCPP2319 as revealed by cellular biomechanics. FEBS J. 2022 Mar;289(6):1603-24. DOI: 10.1111/febs.16247
  • dc.identifier.doi http://dx.doi.org/10.1111/febs.16247
  • dc.identifier.issn 1742-464X
  • dc.identifier.uri http://hdl.handle.net/10230/49192
  • dc.language.iso eng
  • dc.publisher Wiley
  • dc.relation.ispartof FEBS J. 2022 Mar;289(6):1603-24.
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/644167
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/AGL2017-84097-C2-2-R
  • dc.rights © 2021 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.keyword Anticancer activity
  • dc.subject.keyword Biomechanics
  • dc.subject.keyword Blood-brain barrier
  • dc.subject.keyword Cell-penetrating peptide
  • dc.subject.keyword Metastatic breast cancer
  • dc.title The antimetastatic breast cancer activity of the viral protein-derived peptide vCPP2319 as revealed by cellular biomechanics
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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