Anales RANF

P.70 EXTRACELLULAR ADENOSINE PROMOTES GLIOBLASTOMA INVASIVENESS THROUGH THE MODULATION OF MESENCHYMAL STEM CELL SECRETOME C. Giacomelli 1 , D. Pietrobono 1 , C. Martini 1 , M.L. Trincavelli 1 1 . University of Pisa, Italy. Glioblastoma (GBM) is an aggressive, fast-growing brain tumor. Mesenchymal stem cells (MSCs) exhibit tropism for tumor microenvironment, influencing tumor progression. Adenosine (ADO), a purine nucleoside, reaches high concentrations and activates signaling pathways involved in cancer cell proliferation and invasiveness. The activity of specific adenosine receptor (AR) subtypes on glioma cells have been widely explored. However, the effects of extracellular ADO on glioma aggressive traits is still unclear as well as its role on cancer cells-MSC communication. Herein, human U343MG cells were used as a model to investigate the cell proliferation, motility and the expression of epithelial-mesenchymal transition (EMT)-related genes in response to ADO. ADO did not alter U343MG growth rate and migratory capacity. However, ADO was able to induce the transcription of EMT master-gene (Snail, Slug, and ZEB1) without promoting a complete transition. These effects were related to the ability of ADO to significantly modify the equilibrium of different intracellular signaling pathways. High extracellular ADO concentration may also affect MSC modifying their interplay with glioma cells. In these respect, the modification of glioma cell proliferation, migration and expression of EMT-related genes were analyzed after the treatment with MSC-conditioned medium (CM). ADO modified the secretion of pro-inflammatory cytokine from BM-MSC. The CM promoted the increase of glioma motility and induced a partial phenotypic change of glioblastoma cells. In conclusion, these results demonstrate that ADO may affect glioma biology directly and through the modulation of the paracrine factors released by BM-MSCs. The modification of pivotal intracellular signaling pathways after the ADO chronic exposure may promote EMT highlighting the importance of the extracellular ADO levels in the control of glioma aggressiveness. Supported by PRIN 2015, 2015E8EMCM_007