• adenosine receptors
• adenosina
• microambiente tumorale
• ARs
• ADK
• ENTs
• glioblastoma
• adenosine
• tumor microenvironment

Glioblastoma is an aggressive brain tumor, associated with poor prognosis. Adenosine (Ado) plays a key role in the brain, particularly in the tumor microenvironment (TME). Thus, the study of the enzymes implicated in Ado metabolism and transport can help to understand the glioblastoma biology and find new therapeutic approaches. In this thesis, we analyzed the effects of Ado and Neca, which is a non-selective adenosine receptor agonist, on gene expression and protein expression of the actor of purine metabolism in human glioblastoma cells (U343) and bone-marrow-derived mesenchymal stem cells (BM-MSCs). Then, the U343 and BM-MSC cross-talk was investigated by the means of the conditioned medium technique. Specifically, the influence of U343 secretome on BM-MSC response to Ado treatments was analyzed by immunofluorescence. The results demonstrated that the presence of high levels of Ado in the TME can oppositely modify the expression of its metabolism and transport proteins in U343 and BM-MSCs. The U343 cells internalized purine probably to increase its energetic state and proliferation rate. Conversely, the BM-MSCs promoted the maintenance of high extracellular Ado levels supporting the growth of tumor cells. In conclusion, the nucleoside may affect the glioma biology directly and through the modulation of the paracrine factors released by the MSC demonstrating the importance to deeply investigate the role of soluble factors of TME to find new potential therapeutic targets.