title: Exosomes from human colorectal cancer induce a tumor-like behavior in colonic mesenchymal stromal cells.
abstract: BACKGROUND
  Cancer cells, including colorectal cancer ones (CRC), release high amounts of nanovesicles (exosomes), delivering biochemical messages for paracrine or systemic crosstalk. Mesenchymal stromal cells (MSCs) have been shown to play contradicting roles in tumor progression.
  
  
  RESULTS
  CRC exosomes induce in cMSCs: i) atypical morphology, higher proliferation, migration and invasion; ii) formation of spheroids; iii) an acidic extracellular environment associated with iv) a plasma membrane redistribution of vacuolar H+-ATPase and increased expression of CEA. Colon cancer derived MSCs, which were isolated from tumor masses, produce umbilicated spheroids, a future frequently observed in the inner core of rapidly growing tumors and recapitulate the changes observed in normal colonic MSCs exposed to CRC exosomes.
  
  
  METHODS
  Tissue specific colonic (c)MSCs were exposed to primary or metastatic CRC exosomes and analysed by light and electron microscopy, proliferation in 2D and 3D cultures, migration and invasion assays, Western blot and confocal microscopy for vacuolar H+-ATPase expression.
  
  
  CONCLUSIONS
  CRC exosomes are able to induce morphological and functional changes in colonic MSCs, which may favour tumor growth and its malignant progression. Our results suggest that exosomes are actively involved in cancer progression and that inhibiting tumor exosome release may represent a way to interfere with cancer.
authors.affiliation: Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Lugini
authors.affiliation: Department of Ematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Valtieri
authors.affiliation: Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Federici
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Cecchetti
authors.affiliation: Department of Technology and Health, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Meschini
authors.affiliation: Department of Technology and Health, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Condello
authors.affiliation: Department of Ematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Signore
authors.affiliation: Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fais
mesh_terms: D001706:Biopsy; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology*; D015179:Colorectal Neoplasms / Q000378:metabolism*; D018450:Disease Progression; D055354:Exosomes / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006863:Hydrogen-Ion Concentration; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010641:Phenotype; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism
chemical_list: D025262:Vacuolar Proton-Translocating ATPases
keywords: CEA; colorectal cancer; exosomes; mesenchymal stromal cells; vacuolar H+-ATPase