Ectonucleotidases in Tumor Cells and Tumor-Associated Immune Cells: An Overview

Figure 1

Ectonucleotidases in glioma progression. Glioma cells exhibit low ATP/ADP hydrolysis and a high AMP hydrolysis activity [91]. The inversion of extracellular nucleotide metabolism may favor extracellular ATP and adenosine accumulation within the tumor [51, 52, 66]. ATP could induce neuronal toxicity [90], glioma cell proliferation [88], and recruitment of immune cells by inducing the release of proinflammatory factors by tumor cells, such as MCP-1 and IL-8 [99]. Upon reaching the tumor, different stimuli modulate macrophage to M2 phenotype [100, 101], and studies from our laboratory showed that ectonucleotidases are involved in the differentiation of macrophages [24]. The glioma cells exhibit NPP1 on the plasma membrane [94]; this enzyme generates AMP that is toxic for gliomas [74] but is the substrate for the ecto-5′-NT/CD73 which is highly expressed in glioma [74]. Ado, product of AMP hydrolysis could induce tumor cell proliferation, angiogenesis, and immunosuppression [56]. Therefore, the ATP and its hydrolytic products could be closely related to the immune responses involved in the glioma progression.