Exosomes from human colorectal cancer induce a tumor-like behavior in colonic mesenchymal stromal cells

// Luana Lugini 1 , Mauro Valtieri 2 , Cristina Federici 1 , Serena Cecchetti 3 , Stefania Meschini 4 , Maria Condello 4 , Michele Signore 2 , Stefano Fais 1 1 Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanita, Rome, Italy 2 Department of Ematology, Oncology and Molecular Medicine, Istituto Superiore di Sanita, Rome, Italy 3 Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita, Rome, Italy 4 Department of Technology and Health, Istituto Superiore di Sanita, Rome, Italy Correspondence to: Stefano Fais, email: stefano.fais@iss.it Keywords: colorectal cancer, exosomes, mesenchymal stromal cells, vacuolar H+-ATPase, CEA Received: December 16, 2015      Accepted: June 29, 2016      Published: July 13, 2016 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. Materials and 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.