High levels of extracellular ATP lead to chronic inflammatory response in melanoma patients

• Published in: Journal of cellular biochemistry Vol. 119; no. 5; pp. 3980 - 3988
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.05.2018
• Subjects: Adenosine; Adenosine diphosphate; Adenosine triphosphate; Adenosine Triphosphate - blood; Adult; AMP; ATP; Cancer; Chronic Disease; Cytokines; Female; Humans; Hydrolysis; Immune response; Immune system; Inflammation; Inflammation - blood; Inflammatory response; Interleukin-10 - blood; Interleukins; Lymphocytes; Male; Melanoma; Melanoma - blood; Melanoma - pathology; Metastases; Metastasis; Middle Aged; Neoplasm Proteins - blood; Nucleosides; Nucleotides; Patients; Platelets; Public health; purinergic system; Skin cancer; Skin Neoplasms - blood; Skin Neoplasms - pathology; Tumor cells; skin cancer; cytokines; purinergic system; inflammation
• ISSN: 0730-2312; 1097-4644; 1097-4644
• DOI: 10.1002/jcb.26551

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. The presence of high ATP levels in micro‐environment take inflammatory process in melanoma patients even after tumor removal. Deregulation in the metabolism of nucleotides and uncompensated inflammatory profile are present in CM patients even after tumor removal. The purinergic system develops a chronic inflammatory micro‐environment and this can influence directly on relapse or metastasis.