Metastatic breast cancer is a life threatening condition posing many challenges for the pharmaceutical development of effective chemotherapeutics. While the targeted treatment of localized breast masses is improving, metastatic lesions outside the breast, particularly in the brain, increase in their incidence. Management of breast cancer brain metastatic lesions requires drugs that can recognize cancer cells and accumulate efficiently in intracranial tissues after overcoming the blood-brain-barrier (BBB). New therapeutic approaches for breaching the BBB in metastatic breast cancer are thus on demand.
This study shows a potential dual role of the natural antimicrobial plant defensin PvD1 on human breast and brain endothelial cells: the ability in interfering with breast solid tumors’ formation and the control of breast cancer cells’ adhesion to human brain endothelial cells. By using atomic force microscopy (AFM, imaging and SCFS), zeta potential and fluorescence spectroscopy techniques our results suggest that PvD1 internalizes in cancer cells but remains in the membrane of brain cells with no significant damage to its structure and biomechanical properties. PvD1 is capable of suppressing cell-to-cell adhesion by promoting de-adhesion of tumor cells and preventing breast tumor cells’ attachment to endothelial brain cells.
PvD1 is a potential alternative strategy for metastatic breast cancer treatment with an innovative therapeutic activity based on the manipulation of biomechanical properties of tumor cells and suppression of their adhesion to the BBB surface.
Acknowledgements: This work was supported by a grant from Laço (Portugal). The authors thank Fundação para a Ciência e a Tecnologia (FCT I.P., Portugal) and Marie Skłodowska-Curie Research and Innovation Staff Exchange (RISE) for funding- PTDC/BBB-BQB/1693/2014 and call H2020-MSCA-RISE-2014, Grant agreement 644167, 2015-2019, respectively, and acknowledge the financial support of the Brazilian agencies CNPq, CAPES, FAPERJ (E-26/203.090/2016; E-26/202.132/2015). Tiago Figueira, Filipa Oliveira and Diana Gaspar acknowledge FCT I.P. for fellowships SFRH/BD/5283/2013, PD/BD/135046/2017 and SFRH/BPD/109010/2015.