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

Abstract

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.

Bifunctional Cx43 Mimic Peptide Grafted Hyaluronic Acid Hydrogels Inhibited Tumor Recurrence and Stimulated Wound Healing for Postsurgical Tumor Treatment

“…[ 38 ] The wound microenvironment after tumor excision is usually a chronic inflammatory microenvironment, and high levels of ATP in the microenvironment induce macrophages to release large amounts of pro‐inflammatory factors. [ 16 ] It has been reported that gap junction molecular Cx43 can affect host inflammation responses and cell migration during wound healing. [ 39 ] Connexin hemichannels are important channels for ATP releasing in many cells, including inflammatory cells, endothelial cells, and fibroblasts.…”

“…High levels of extracellular ATP induce macrophages to initiate an immune response and release a large number of inflammatory factors, which may lead to tumor recurrence. [ 16 ] Thus, modulating the ATP release from cells may be a feasible way to control the inflammation responses in the wound sites. It has been reported that JM2 could reduce the concentration of extracellular ATP.…”

The Impact of Purinergic System Enzymes on Noncommunicable, Neurological, and Degenerative Diseases

“…The enzymatic chain responsible for ATP hydrolysis and adenosine production, present in all immune and vascular cells, has an important role in the control or promotion of inflammation in tumors [ 117 ]. This is because of an exuberant immune/inflammatory response, not adequately balanced by endogenous mechanisms of homeostatic control that can lead to persistent and abnormal forms of collateral tissue damage [ 118 ].…”

Increased Graft Survival through Ectonucleotidases Modulation in Platelets and Lymphocytes of Kidney Transplanted Patients

“…The molecules, receptors and ectoenzymes of the purinergic system could be an alternative measure regarding the process of combating graft rejection, since this system has important participants in metabolic processes, such as inflammatory and immunological responses [4][5][6]. Extracellular adenosine triphosphate (ATP) is either passively released by necrotic cells during cell damage, or it is actively released by activated immune cells and by apoptotic cells [7,8].…”

“…ATP is mainly associated with pro-inflammatory response; however, adenosine has opposite effects, limiting inflammation by suppressing the actions of immune cells [4,[12][13][14][15][16]. Knowing that the purinergic signaling is involved in the inflammatory response that leads to acute kidney rejection and chronic allograft dysfunction, we evaluated the modulation of purinergic signaling components in patients after kidney transplantation.…”