| Autor: |
Skalska J; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal. macastanho@medicina.ulisboa.pt., Oliveira FD; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal. macastanho@medicina.ulisboa.pt., Figueira TN; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal. macastanho@medicina.ulisboa.pt., Mello ÉO; Laboratório de Fisiologia e Bioquímica de Microrganismos do Centro de Biociências e Biotecnologia da Universidade Estadual do Norte Fluminense Darcy Ribeiro, Rio de Janeiro, Brazil., Gomes VM; Laboratório de Fisiologia e Bioquímica de Microrganismos do Centro de Biociências e Biotecnologia da Universidade Estadual do Norte Fluminense Darcy Ribeiro, Rio de Janeiro, Brazil., McNaughton-Smith G; CEAMED - Centro Atlántico del Medicamento, S.A., San Cristobal de La Laguna, S/C Tenerife, Spain., Castanho MARB; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal. macastanho@medicina.ulisboa.pt., Gaspar D; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal. macastanho@medicina.ulisboa.pt. |
| Abstrakt: |
One of the most important causes of failure in tumour treatment is the development of resistance to therapy. Cancer cells can develop the ability to lose sensitivity to anti-neoplastic drugs during reciprocal crosstalk between cells and their interaction with the tumour microenvironment (TME). Cell-to-cell communication regulates a cascade of interdependent events essential for disease development and progression and can be mediated by several signalling pathways. Exosome-mediated communication is one of the pathways regulating these events. Tumour-derived exosomes (TDE) are believed to have the ability to modulate TMEs and participate in multidrug resistance mechanisms. In this work, we studied the effect of the natural defensin from common bean, PvD 1 , on the formation of exosomes by breast cancer MCF-7 cells, mainly the modulatory effect it has on the level of CD63 and CD9 tetraspanins. Moreover, we followed the interaction of PvD 1 with biological and model membranes of selected composition, by biophysical and imaging techniques. Overall, the results show that PvD 1 induces a dual effect on MCF-7 derived exosomes: the peptide attenuates the recruitment of CD63 and CD9 to exosomes intracellularly and binds to the mature exosomes in the extracellular environment. This work uncovers the exosome-mediated anticancer action of PvD 1 , a potential nutraceutical agent. |
