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High levels of extracellular ATP lead to chronic inflammatory response in melanoma patients
Author(s) -
Manica Aline,
Da Silva Alexsandra Martins,
Cardoso Andreia Machado,
Moreno Marcelo,
Leal Daniela Bittencourt,
Dutra Da Silva Anielen,
Schetinger Maria Rosa Chitolina,
Morsch Vera Maria Melchiors,
Bagatini Margarete Dulce
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26551
Subject(s) - purinergic receptor , extracellular , immune system , adenosine , melanoma , platelet , lipopolysaccharide , immunology , adenosine triphosphate , purinergic signalling , inflammation , cancer research , medicine , chemistry , biochemistry , receptor , adenosine receptor , agonist
Skin cancer represents a serious public health problem and melanoma is considered the most significant due to its high metastasis capacity. Evasion mechanisms are the main characteristic of these tumor cells to escape of immune response. Extracellular nucleotides and nucleosides play an important role in inflammatory and immune responses. In this study, we analyzed the expression and activity of purinergic system enzymes in platelets and lymphocytes, ATP levels quantification, as well the level of pro and anti‐inflammatory interleukins in the serum of 23 patients with surgical melanoma removal (CM group) and 23 control subjects (CT group). Results showed a decrease in ATP, ADP, and AMP hydrolysis and an increase in ATP levels quantification in CM group. The pro‐inflammatory cytokines were elevated in CM group when compared to CT group. These results suggest an inflammatory process, even after surgical removal, due to elevated extracellular ATP levels. Besides, CM group displayed an increase in IL‐10 levels and an increased in ADA activity in platelets and lymphocytes. Once adenosine and IL‐10 are anti‐inflammatory molecules, these results indicate a down‐regulation of immune system front to malignant process. The alteration in nucleotide and nucleoside hydrolysis reinforces the purinergic systems role in this cancer. Therefore, even after surgical removal, the purinergic system can develop a chronic inflammatory micro‐environment that can influence directly on relapse or metastasis.