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

Oliveira, Filipa; Cavaco, Marco; Figueira, Tiago Nascimento; Valle, Javier; Neves, Vera; Andreu, David; Gaspar, Diana; Castanho, Miguel A. R. B.

http://hdl.handle.net/10451/57522

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Authors

Oliveira, Filipa

Cavaco, Marco

Figueira, Tiago Nascimento

Castanho, Miguel A. R. B.

Abstract(s)

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.

Description

© 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.