Avaliação do sistema purinérgico e inflamação em pacientes com câncer de mama

Abstract

Breast cancer is a multifactorial disease caused by a deregulation in the cell cycle, being con-sidered a global public health problem due to its high incidence and high mortality rate. The cellular mechanisms involved in the process of cell evasion trigger different inflammatory and immunological processes, among these, the purinergic system, is involved in tumor develop-ment, also acting as an immunological and inflammatory modulator. Considering these cellular modulations, new diagnostic and therapeutic strategies have been studied. Objective: To eval-uate the enzymatic activity of components of the purinergic system and the inflammatory pro-file in blood samples from individuals with breast cancer and from control individuals. Method: This is a cross-sectional, quantitative analysis, case-and-control study. The study consisted of 72 individuals divided into two groups: control group (n= 35) and breast cancer group (n= 37). The enzymatic activity of ectonucleotidases (CD39, CD73 and ADA) in lymphocytes, the se-rum quantification of extracellular ATP, the profile of inflammatory cytokines (IL-2, IL-4, IL-6, IL-10) and inflammatory mediators were evaluated. (TNF and INF-γ). Results: The results showed an increase in ATP (p=0.0273), ADP (p= 0.0358) and AMP (p=0.0060) hydrolysis in the breast cancer group. ATP quantification was increased in the breast cancer group (p=0.0002). Regarding interleukins, IL-2 (p=0.0013), IL-4 (p=0.0457) and TNF (p=0.0156) were reduced in the breast cancer group compared to the control group. Conclusion: In sum-mary, we show for the first time significant alterations of the entire purinergic pathway involv-ing the hydrolysis of ATP to Ado, represented by the increased hydrolysis of ATP, ADP and AMP in a patient with BC, in addition to the increase in extracellular ATP. Thus, our results suggest a pro-inflammatory and immunosuppressive environment, since it is known that extra-cellular ATP has a pro-inflammatory function and actively participates in carcinogenesis, while the high hydrolysis of ATP, ADP and AMP can trigger the formation of high concentrations disease, signaling worse outcomes in cancer progression and reinforcing the role of the puriner-gic system in breast cancer. As for inflammatory interleukins, the decrease in TNF and IL-2 in the breast cancer group stands out, favoring cell apoptosis and anti-tumor action, respectively, contributing to tumor progression. However, our findings become important for future research that seeks new therapeutic and diagnostic possibilities for the management of patients with breast cancer.