Research reveals plant defensin impact on breast tumor cells’ adhesion to the blood-brain barrier cells

send to a friend share this

Research reveals plant defensin impact on breast tumor cells’ adhesion to the blood-brain barrier cells

Tuesday, 06.02.2018

Researchers from Instituto de Medicina Molecular João Lobo Antunes revealed the anticancer activity of PvD1, a plant defensin isolated from the common bean, on breast tumor cells and the ability of this defensin in hampering tumor cells’ adhesion to the blood-brain barrier cells. For this study, scientists combined spectroscopic techniques with atomic force microscopy (AFM) for evaluating the biomechanical changes that cells suffer upon PvD1 contact. This work, recently published in Nanoscale, will contribute for the design of new peptide-based antitumoral therapies targeting metastatic breast cancer, a disease with limited treatment options.

 

Authors and Affiliations:

Tiago N. Figueira,  Filipa D. Oliveira,  Inês Almeida,  Érica O. Mello,  Valdirene M. Gomes,  Miguel A. R. B. Castanho and  Diana Gaspar

Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, Lisbon 1649-028, Portugal

Laboratório de Fisiologia e Bioquímica de Microrganismos do Centro de Biociências e Biotecnologia da Universidade Estadual do Norte Fluminense Darcy Ribeiro, Avenida Alberto Lamego 2000, Campos dos Goytacazes, Rio de Janeiro, Brazil

 

Abstract:

Metastatic 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.

 

Journal: Nanoscale. 2017 Nov 9;9(43):16887-16899. doi: 10.1039/c7nr05872a.

 

Link: http://pubs.rsc.org/en/Content/ArticleLanding/2017/NR/C7NR05872A#!divAbstract