THE ROLE OF PURINERGIC SIGNALING IN THE PATHOPHYSIOLOGY OF CERVICAL CANCER

Introduction: Cervical Cancer (CeCa) is the fourth most common type of cancer incidence in the world female population. There are numerous different factors involved in this type of cancer, including intrinsic factors related to the inflammatory process, such as extracellular nucleotides and adenosine – compounds of the purinergic system. Objective: To evaluate the activity and expression of enzymes that hydrolyze adenine nucleotides and nucleosides in lymphocytes from patients diagnosed with CeCa. Methods: Cross-sectional study with included female patients between 18 and 70 years of age; without previous surgical removal of the tumor or that still have not started pharmacological treatment at the moment of participation in the research and which have neither present hypertension, diabetes or chronic inflammatory disease. NTPDase (nucleoside triphosphate diphosphohydrolases) and total ADA (adenosine deaminase) from 10 patients with different stages of cervical intraepithelial neoplasia (CINs I, CIN II, CIN III) were analyzed Results: Both ATP and ADP hydrolysis were increased in patients with CeCa – suggesting that signaling and the purinergic pathway play an important role in this type of cancer. On the other hand, ADA activity was significantly decreased in the cancer patients – in contrast to the control group. This result is quite intriguing, given the numerous reports of increased ADA activity in a wide range of individuals with cancer. Some studies, however, found low lymphocyte ADA activities in cancer patients – as in bladder cancer, for example. It is likely that this low lymphocyte ADA activities might have acted as a sensitive indicator of suppressed cellular immunity and this is consistent with the characteristics of CeCa. This type of cancer promotes an immunosuppressive microenvironment through increasing production of immunosuppressive cytokines and the downregulation of human class I leukocyte antigen system (HLAI), which serves as an immune evasion mechanism – promoted by the persistent infection of high-risk HPV types – and that ultimately leads to immune evasion by cervical carcinoma. Conclusion: Our results showed that tumor microenvironment of CeCa is rich in ATP and adenosine – which demonstrates that the purinergic system might play an important role concerning the mechanisms that control cell growth and death in cancer – while the low ADA activity found matches the immunosuppressive microenvironment of CeCa.