Anales RANF

S4-01 INFLUENCE OF DIFFERENT PURINE RECEPTORS ON THE DIFFERENTIATION POTENTIAL OR MALIGNANCY OF NORMAL OR CANCEROUS MESENCHYMAL STEM CELLS, RESPECTIVELY M. Carluccio 1,2 , S. Ziberi 1,2 , M. Zuccarini 1 , P. Giuliani 1 , F. Caciagli 1 , P. Di Iorio 1 , R. Ciccarelli 1,2 . 1 University of Chieti-Pescara, Chieti. Italy. 2 StemTeCh Group, Chieti, Italy. Mesenchymal Stromal/Stem Cells (MSCs) are multi-potent cells located in differentiated organs to maintain tissue homeostasis. Stem-like cells are present also in tumors and contribute to their malignancy. Preclinical/clinical studies demonstrated that differentiation capabilities/ aggressiveness of normal/tumor MSCs, respectively, can be modulated by endogenous substances/ related drugs. Purines are ancestral molecules released from cells, including MSCs, whose extracellular concentration is increased during tissue injury or in tumor microenvironment. Hence, endogenous/exogenous purines may influence MSC properties by interacting with their own receptors. In particular, both adenosine and ATP regulate MSC osteogenic differentiation. Indeed, the A1 adenosine receptor stimulation enhances osteogenesis while decreasing adipogenesis in MSCs derived from human dental or adipose tissue, by activating the Wnt signal. Also the stimulation of P2X7 receptor (P2X7R) by endogenous ATP contributes to cell osteogenic differentiation, increasing the number/expression of these receptors. Conversely, P2X7R pharmacological stimulation by BzATP, mimicking the effects of high ATP levels occurring during tissue injury, decreases receptor expression/activity, thus impairing MSC commitment towards osteogenesis. Thereby, our findings confirm the fundamental role played by local extracellular purines in bone healing/remodeling that should be carefully monitored to favor/increase MSC usefulness in bone regenerative medicine. On the other hand, in human stem-like cells from glioblastoma (GBM) surgical specimens P2X7R activation by 500- 1000μM BzATP exerted a cytotoxic effect while lower concentrations (100- 200μM) increased cell migration/invasion and the expression of epithelial-to-mesenchymal transition- related genes and of P2X7R. Since in GBM microenvironment there are ATP levels able to activate P2X7R, our data support a role for these receptors in GBM recurrence/invasiveness.