Original article Ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP) and adenosine deaminase (ADA) activities in prostate cancer patients: Influence of Gleason score, treatment and bone metastasis Vanessa Battisti a, *, Lie ´ si D.K. Maders a , Margarete D. Bagatini a , Iara E. Battisti b , Luziane P. Belle ´ c , Karen F. Santos a , Paula A. Maldonado a , Gustavo R. Thome ´ a , Maria R.C. Schetinger a , Vera M. Morsch a, * a Departamento de Quı´mica, Centro de Cieˆncias Naturais e Exatas, Universidade Federal de Santa Maria, Campus Universita ´rio, 97105-900 Santa Maria, RS, Brazil b Departamento de Matema ´tica, Universidade Federal da Fronteira Sul, Cerro Largo, RS, Brazil c Departamento de Ana ´lises Clı´nicas, Centro de Cieˆncias da Sau ´de, Universidade Federal de Santa Maria, Campus Universita ´rio, 97104-900 Santa Maria, RS, Brazil 1. Introduction Prostate cancer (PCa) is the most common non-cutaneous cancer in men and the second most common form of cancer death [1]. The factors that determine the risk of developing clinical prostate cancer and particularly the risk of developing aggressive disease are not well characterized [2]. The mechanism of prostate carcinogenesis involves a combination of both acquired factors and inherited genetic predisposition, a concept supported by extensive evidences [3,4]. The greatest known risk factor is age, with a very low risk of developing the disease in men under 50 and rising risk with increasing age thereafter; nearly 65% of cases occur in men aged 65 and older [5]. The morphological appearance of cancer cells reflecting distinct degrees of differentiation was elegantly analyzed and classified by Gleason [6,7] into the currently used standard grading system, which is based on the degree of glandular differentiation and the interaction of the malignant glands with stroma [8]. Although great advances have been made in the treatment of PCa in recent years, questions still remain concerning the optimal treatment strategy for both localized disease and metastatic disease (mainly bone metastases). This lack of a standard treatment may be partly attributed to variations in the risk of disease progression among patients [9]. A vast majority (90%) of PCa deaths occurs in patients with bone metastases [10]. Men with advanced PCa are at high risk of developing bone metastases resulting in clinically significant skeletal morbidity and severe bone pain. Extracellular adenine nucleotides and nucleosides act as signaling molecules involved in a wide spectrum of biological effects [11]. A variety of pathophysiological responses to nucleo- tides have been described, including roles in cell proliferation and growth [12] as well as induction of apoptosis [13]. The control of circulating nucleotide levels is important in the maintenance of the physiological nucleotide-mediated signaling process. This control is exerted by a family of enzymes that hydrolyzes such nucleotides and consequently generates their respective metabolites [14]. These ecto-enzymes include the ecto-nucleoside triphosphate diphosphohydrolase (Ecto-NTPDase) and ectonucleotide pyropho- sphatase/phosphodiesterase (E-NPP) families as well as 5 0 - nucleotidase and adenosine deaminase (ADA) [15]. E-NPP (EC 3.1.4.1) is responsible for hydrolyzing 5 0 -phospho- diester bonds in nucleotides and their derivatives, where both purines and pyrimidines serve as substrates, resulting in the Biomedicine & Pharmacotherapy 67 (2013) 203–208 ARTICLE INFO Article history: Received 21 November 2012 Accepted 7 December 2012 Keywords: Prostate cancer Ectonucleotide pyrophosphatase/ phosphodiesterase Adenosine deaminase ABSTRACT The relation between adenine nucleotides and cancer has already been described in literature. Considering that the enzymes ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP) and adenosine deaminase (ADA) act together to control nucleotide levels, we aimed to investigate the role of these enzymes in prostate cancer (PCa). E-NPP and ADA activities were determined in serum and platelets of PCa patients and controls. We also verified the influence of the Gleason score, bone metastasis and treatment in the enzyme activities. Platelets and serum E-NPP activity increased, whereas ADA activity in serum decreased in PCa patients. In addition, Gleason score, metastasis and treatment influenced E-NPP and ADA activities. We may propose that E-NPP and ADA are involved in the development of PCa. Moreover, E-NPP and ADA activities are modified in PCa patients with distinct Gleason score, with bone metastasis, as well as in patients under treatment. ß 2013 Elsevier Masson SAS. All rights reserved. * Corresponding authors. Centro de Cie ˆncias Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil. Fax: +55 55 3220 8978. E-mail address: battistivanessa@gmail.com (V. Battisti). Available online at www.sciencedirect.com 0753-3322/$ – see front matter ß 2013 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.biopha.2012.12.004