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AMP hydrolysis reduction in blood plasma of breast cancer elderly patients after different treatments

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Abstract

Adenine nucleotides are important signaling molecules that mediate biological functions in many conditions, including cancer. The enzymes CD39 and CD73 produce adenosine in the extracellular milieu that has a very important role in tumor development. This study aimed to evaluate nucleotide hydrolysis in the plasma blood of breast cancer elderly patients. In this prospective cohort study, we investigated the ectonucleotidases activity in breast cancer elderly patients, at the moment of diagnosis and after treatment. Control group consisted of elderly women without cancer diagnostic. The nucleotide hydrolysis assay was performed by the malachite green method and used ATP, ADP, or AMP as substrates. Paired t test or Wilcoxon rank-sum test was used. Our data showed that breast cancer patients presented high levels of ATP and AMP hydrolyses when compared to control group at the moment of diagnosis. When analyzing the differences between the samples at the time of diagnostic and 6 months after treatment, we observed a significant reduction on CD73 activity after all treatments used: surgery, chemotherapy, radiotherapy, or hormone therapy. The results with APCP, a specific CD73 inhibitor, showed that the AMP hydrolysis was inhibited in all conditions evaluated. We observed a diminished ADPase activity in the patients without metastasis when compared to metastatic breast cancer patients. The results showed that AMP hydrolysis was reduced in the blood plasma of breast cancer elderly patients after different treatments. This study strengthens the potential role of CD73 enzyme as a biomarker for breast cancer treatment response.

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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) Finance Code 001, FAPERGS (PPSUS-17/2551-0001455-3) and FINEP (Financiadora de Estudos e Projetos) research grant “Implantação, Modernização e Qualificação de Estrutura de Pesquisa da PUCRS” (PUCRSINFRA) # 01.11.0014-00. We thank MD Mathias A. Kunde for the help in blood collection.

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  1. FernandaValente Gheler and Angélica Regina Cappellari are first authors.

Authors and Affiliations

  1. Programa de Pós-Graduação em Biologia Celular e Molecular, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brasil

    Fernanda Valente Gheler, Angélica Regina Cappellari & Fernanda Bueno Morrone

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

    Daiana Renck, Liliana Rockenbach & Fernanda Bueno Morrone

  3. Laboratório de Farmacologia Aplicada, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, Partenon, Porto Alegre, RS, 90619-900, Brasil

    Julia Brandt de Souza, Ana Paula Franco Lambert & Fernanda Bueno Morrone

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

    Renan Oliveira de Melo, Barbara Zanesco Moehlecke & Carolina Aiko Moriguchi

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

    Paula Engroff

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Contributions

F.B.M, D.R, and A.R.C participated in the research design. F.V.G, A.R.C, J.B.S, R.O.M, B.Z.M, C.A.M, and L.R conducted the experiments. PE, A.P.F.L, and A.R.C performed data analysis. F.V.G, F.B.M, A.R.C, L.R, and wrote or contributed to the writing of the manuscript.

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Correspondence to Fernanda Bueno Morrone.

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This study was carried out following the Declaration of Helsinki, and all subjects signed an Informed Consent Form previously approved by the Local Ethics Committee. The study was approved by the Ethical Committee of the Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre (CAAE: 65653717.0.0000.5336).

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Gheler, F.V., Cappellari, A.R., Renck, D. et al. AMP hydrolysis reduction in blood plasma of breast cancer elderly patients after different treatments. Mol Cell Biochem 476, 3719–3727 (2021). https://doi.org/10.1007/s11010-021-04199-x

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