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Hydrolysis of ATP, ADP, and AMP is increased in blood plasma of prostate cancer patients

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Abstract

Prostate cancer is among the major malignancies that affect men around the world. Adenine nucleotides are important signaling molecules that mediate innumerous biological functions in pathophysiological conditions, including cancer. These molecules are degraded by several ectoenzymes named ectonucleotidases that produce adenosine in the extracellular medium. Some of these ecto-enzymes can be found in soluble in the blood stream. Thus, the present study aimed to evaluate the hydrolysis of adenine nucleotides (ATP, ADP, and AMP) in the plasma blood of patients with prostate cancer. Peripheral blood samples were collected, and questionnaires were filled based on the clinical data of the medical records. The nucleotide hydrolysis was performed by Malachite Green method using ATP, ADP, and AMP as substrates. Plasma from prostate cancer patients presented an elevated hydrolysis of all nucleotides evaluated when compared to healthy individuals. NTPDase inhibitor (ARL67156) and the alkaline phosphatase inhibitor (levamisole) did not alter ATP hydrolysis. However, AMP hydrolysis was reduced by the CD73 inhibitor, APCP, and by levamisole, suggesting the action of a soluble form of CD73 and alkaline phosphatase. On microvesicles, it was observed that there was a low expression and activity of CD39 and almost absent of CD73. The correlation of ATP, ADP, and AMP hydrolysis with clinic pathological data demonstrated that patients who received radiotherapy showed a higher AMP hydrolysis than those who did not, and patients with lower clinical stage (CS-IIA) presented an elevated ATP hydrolysis when compared to those with more advanced clinical stages (CS-IIB and CS-III). Patients of all clinical stages presented an elevated AMPase activity. Therefore, we can suggest that the nucleotide hydrolysis might be attributed to soluble ecto-enzymes present in the plasma, which, in a coordinate manner, produce adenosine in the blood stream, favoring prostate cancer progression.

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Acknowledgements

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior, Brasil (CAPES-001) scholarships, CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) scholarships, FAPERGS (PPSUS-17/2551-0001455-3), FAPERGS/PRONEX (16/2551-0000473-0), FAPERGS/PqG 17/2551-000970-3PUCRS (Pontifícia Universidade Católica do Rio Grande do Sul), LACOG (Latin American Cooperative Oncology Group), FINEP (Financiadora de Estudos e Projetos) research grant “Implantação, Modernização e Qualificação de Estrutura de Pesquisa da PUCRS” (PUCRSINFRA) # 01.11.0014-00, INCT-MCTI/CNPq/CAPES/FAPERGS (project number 465671/2014-4), CNPq/PQ (project number 302879/2017-0), FAPERGS PQG (project number 17/2551-0000 970-3), and FAPERGS/PRONEX (project number 16/2551-0000473-0).

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Authors and Affiliations

  1. Escola de Medicina, Programa de Pós-Graduação em Medicina e Ciências da Saúde, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Carla Fernanda Furtado Gardani & Fernanda Bueno Morrone

  2. Escola de Ciências, Programa de Pós-Graduação em Biologia Celular e Molecular, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Angélica Regina Cappellari & Fernanda Bueno Morrone

  3. Escola de Ciências, Graduação em Ciências Biológicas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Julia Brandt de Souza

  4. Escola de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Bruna Tertuliano da Silva

  5. Instituto de Geriatria e Gerontologia, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Paula Engroff

  6. Programa de Pós-Graduação em Ciências do Movimento Humano, Escola de Educação Física, Fisioterapia e Dança, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Cesar Eduardo Jacintho Moritz

  7. Programa de Pós-Graduação em Ciências Biológicas—Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Juliete Nathali Scholl, Ana Maria Oliveira Battastini & Fabrício Figueiró

  8. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Ana Maria Oliveira Battastini & Fabrício Figueiró

  9. Escola de Ciências da Saúde, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Fernanda Bueno Morrone

  10. Laboratório de Farmacologia Aplicada/Escola de Ciências da Saúde, Pontificia Universidade Catolica do Rio Grande do Sul, Avenida Ipiranga, 6681, Partenon, Porto Alegre, RS, 90619-900, Brazil

    Fernanda Bueno Morrone

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  1. Carla Fernanda Furtado Gardani
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Correspondence to Fernanda Bueno Morrone.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the Ethical Committee of the Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre (CAAE: 62424416.0.0000.5336) and by the Ethical Council of the Hospital São Vicente de Paulo-CACON, Cruz Alta, RS (2017-001).

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Carla Fernanda Furtado Gardani and Angélica Regina Cappellari are first authors.

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Gardani, C.F.F., Cappellari, A.R., de Souza, J.B. et al. Hydrolysis of ATP, ADP, and AMP is increased in blood plasma of prostate cancer patients. Purinergic Signalling 15, 95–105 (2019). https://doi.org/10.1007/s11302-018-9642-3

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