| Popis: |
Glioma invasion is a multifactorial process consisting of numerous genetic and physiological alterations, which affect glioma cell interactions with neurons, glia, and vascular cells. Purinergic signaling is emerging as an important component to give invasive potential to glioma cells. Specific purinergic receptor subtypes have been implicated in a variety of biological effects, including proliferation, differentiation, trophic actions and immune/inflammatory responses. Signaling events induced by extracellular nucleotides are controlled by the action of ectonucleotidases. These enzymes operate in concert for the complete nucleotide hydrolysis to nucleoside and represent a powerful manner to control the effects mediated by extracellular purines. It was demonstrated that glioma cell lines have altered extracellular ATP, ADP and AMP catabolism, presenting low rates of extracellular ATP hydrolysis and high rates of extracellular AMP hydrolysis when compared to astrocytes. Therefore, the ATP released by tumor adjacent cells, often damaged by growing tumors or due to ongoing inflammation together with the low glioma ability to hydrolyze extracellular ATP could result in powerful purinergic receptor activation, which in turn modulates glioma cell proliferation and neuronal toxicity. In addition, the high expression and activity of ecto-5ʹ-NT/CD73 in glioma cells and the extracellular adenosine generation could also be involved in the immunosupression process, angiogenesis and glioma invasion. These alterations could have important consequences in the activation of purinergic receptors and modulate events related to glioma advance. Although more studies are necessary, the ectonucleotidases may be considered as new molecular markers of gliomas and future target for pharmacological or gene therapy. |
