title: Proteomic analysis of extracellular vesicles from medullospheres reveals a role for iron in the cancer progression of medulloblastoma.
abstract: BACKGROUND
  Medulloblastoma (MB) is the most common malignant childhood brain tumor with the propensity to disseminate at an early stage, and is associated with high morbidity. New treatment strategies are needed to improve cure rates and to reduce life-long cognitive and functional deficits associated with current therapies. Extracellular Vesicles (EVs) are important players in cell-to-cell communication in health and diseases. A clearer understanding of cell-to-cell communication in tumors can be achieved by studying EV secretion in medullospheres. This can reveal subtle modifications induced by the passage from adherent to non-adherent growth, as spheres may account for the adaptation of tumor cells to the mutated environment.
  
  
  METHODS
  Formation of medullospheres from MB cell lines stabilized in adherent conditions was obtained through culture conditioning based on low attachment flasks and specialized medium. EVs collected by ultracentrifugation, in adherent conditions and as spheres, were subjected to electron microscopy, NanoSight measurements and proteomics.
  
  
  RESULTS
  Interestingly, iron carrier proteins were only found in EVs shed by CSC-enriched tumor cell population of spheres. We used iron chelators when culturing MB cell lines as spheres. Iron chelators induced a decrease in number/size of spheres and in stem cell populations able to initiate in vitro spheres formation.
  
  
  CONCLUSIONS
  This work suggests a not yet identified role of iron metabolism in MB progression and invasion and opens the possibility to use chelators as adjuvants in anti-tumoral chemotherapy.
authors.affiliation: EuroClone S.p.A Research Laboratory, Molecular Biotechnology Centre (MBC), University of Turin, Turin, Italy.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bisaro
authors.affiliation: Centre for Experimental and Clinical Studies CERMS, Azienda Universitaria Ospedaliera Città della Salute e della Scienza Città di Torino, Turin, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Mandili
authors.affiliation: BioDigitalValley srl, Pont-Saint-Martin (AO), Turin, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Poli
authors.affiliation: Department of Molecular Biotechnology and Heath Sciences, University of Turin, Turin, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Piolatto
authors.affiliation: Department of Neuromotor and Biomedical Sciences, Alma Mater University of Bologna, Bologna, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Papa
authors.affiliation: Department of Molecular Biotechnology and Heath Sciences, University of Turin, Turin, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Novelli
authors.affiliation: Department of Neuromotor and Biomedical Sciences, Alma Mater University of Bologna, Bologna, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cenacchi
authors.affiliation: Department of Molecular Biotechnology and Heath Sciences, University of Turin, Turin, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Forni
authors.affiliation: EuroClone S.p.A Research Laboratory, Molecular Biotechnology Centre (MBC), University of Turin, Turin, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Zanini