title: Multidrug resistant tumour cells shed more microvesicle-like EVs and less exosomes than their drug-sensitive counterpart cells.
abstract: BACKGROUND
  Multidrug resistance (MDR) is a serious impediment to cancer treatment, with overexpression of drug efflux pumps such as P-glycoprotein (P-gp) playing a significant role. In spite of being a major clinical challenge, to date there is no simple, minimally invasive and clinically validated method for diagnosis of the MDR phenotype using non-tumour biological samples. Recently, P-gp has been found in extracellular vesicles (EVs) shed by MDR cancer cells. This study aimed to compare the EVs shed by MDR cells and their drug-sensitive cellular counterparts, in order to identify biomarkers of MDR.
  
  
  METHODS
  Two pairs of MDR and drug-sensitive counterpart tumour cell lines were studied as models. EVs were characterized in terms of size and molecular markers and their protein content was investigated by proteomic analysis and Western blot.
  
  
  RESULTS
  We found that MDR cells produced more microvesicle-like EVs and less exosomes than their drug-sensitive counterpart. EVs from MDR cells contained P-gp and presented a different content of proteins known to be involved in the biogenesis of EVs, particularly in the biogenesis of exosomes.
  
  
  CONCLUSIONS
  The determination of the size and of this particular protein content of EVs shed by tumour cells may allow the development of a minimally-invasive simple method of detecting and predicting MDR.
  
  
  CONCLUSIONS
  This work describes for the first time that cancer multidrug resistant cells shed more microvesicle-like EVs and less exosomes than their drug-sensitive counterpart cells, carrying a specific content of proteins involved in EV biogenesis that could be further studied as biomarkers of MDR.
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, 4200-465 Porto, Portugal; ICBAS-UP - Institute of Biomedical Sciences Abel Salazar, University of Porto, 4099-003 Porto, Portugal.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Lopes-Rodrigues
authors.affiliation: NICB - National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland, UK.
authors.forename: Alessio
authors.initials: A
authors.lastname: Di Luca
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, 4200-465 Porto, Portugal; Department of Biological Sciences, FFUP - Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
authors.forename: Diana
authors.initials: D
authors.lastname: Sousa
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, 4200-465 Porto, Portugal.
authors.forename: Hugo
authors.initials: H
authors.lastname: Seca
authors.affiliation: NICB - National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland, UK.
authors.forename: Paula
authors.initials: P
authors.lastname: Meleady
authors.affiliation: NICB - National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Henry
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, 4200-465 Porto, Portugal; Department of Pathology and Oncology, FMUP - Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal.
authors.forename: Raquel T
authors.initials: RT
authors.lastname: Lima
authors.affiliation: NICB - National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: O'Connor
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, 4200-465 Porto, Portugal; Department of Biological Sciences, FFUP - Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal. Electronic address: hvasconcelos@ipatimup.pt.
authors.forename: M Helena
authors.initials: MH
authors.lastname: Vasconcelos
mesh_terms: D055252:Cell-Derived Microparticles / Q000502:physiology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D055354:Exosomes / Q000502:physiology*; D000067128:Extracellular Vesicles / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*
keywords: Extracellular vesicles; Multidrug resistance; Tumour cells