Adenosine is a primordial signalling molecule that has evolved to modulate physiological responses in all mammalian tissues. Due to the breadth of its effects, it is not possible to summarize all of the new developments in our understanding of adenosine receptor physiology even within the past year. Adenosine is released into the extracellular environment from metabolically active or stressed cells. It acts as an important regulatory molecule by binding to specific G-protein-associated A1, A2A, A2B and A3 cell surface receptors. The A1 and A3 receptors are coupled to Gi protein and cause inhibition of adenylate cyclase (AC), whereas A2A and A2B receptor subtypes are coupled to Gs protein and cause an increase in AC activity (Linden, 2001). There is growing evidence that adenosine modulates inflammatory processes and the immune response. The ability of adenosine to suppress lymphocyte-mediated cytolysis of tumor or leukemic cell targets suggests that it might have the ability to suppress the anticancer immune response. This may be particularly important in hypoxic solid tumors, because hypoxia leads to increased adenosine levels . On the other hand, a great variability has been observed in the response to adenosine among normal and cancer cells as a mirror of the different distribution of cell surface adenosine receptors between normal and tumor cells. In view of these hallmarks, the central hypothesis of this proposal is that the clarification of the cellular and biochemical mechanisms of adenosine can be important for the understanding of its possible role in the pathogenesis of tumors. Therefore, the principal goal of this project is to study the ability of adenosine analogues, used alone or in combination with chemotherapic drugs, to mediate cytotoxic/cytostatic response in different normal and tumor cell lines characterized for the presence of adenosine receptors. We believe that the data derived from these studies will lead to new insights in the potential clinical use of these compounds in the development of novel anticancer therapies.
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|Titolo:||Progetto AIRC- Adenosine receptors as mediators of both cell proliferation and cell death. Basis for antitumoral therapies.|
|Data di pubblicazione:||2003|
|Appare nelle tipologie:||08.1 Coordinamento Prog.Ricerca Naz. ed Internaz.|