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Archivio digitale delle tesi discusse presso l’Università di Pisa

Tesi etd-05092021-203924


Tipo di tesi
Tesi di laurea magistrale
Autore
SANTERO, SARA
URN
etd-05092021-203924
Titolo
Microambiente Tumorale nel Glioblastoma: modulazione del sistema purinergico
Dipartimento
FARMACIA
Corso di studi
SCIENZE DELLA NUTRIZIONE UMANA
Relatori
relatore Giacomelli, Chiara
correlatore Russo, Lara
Parole chiave
  • adenosina
  • adenosine
  • adenosine receptors
  • ADK
  • ARs
  • ENTs
  • glioblastoma
  • microambiente tumorale
  • tumor microenvironment
Data inizio appello
26/05/2021
Consultabilità
Non consultabile
Data di rilascio
26/05/2091
Riassunto
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.
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