4.6 Article

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

Journal

MOLECULAR AND CELLULAR BIOCHEMISTRY
Volume 476, Issue 10, Pages 3719-3727

Publisher

SPRINGER
DOI: 10.1007/s11010-021-04199-x

Keywords

Breast cancer; Elderly patients; Plasma blood; Ectonucleotidases; CD39; CD73

Categories

Funding

  1. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - Brasil (CAPES) [001]
  2. FAPERGS [PPSUS-17/2551-0001455-3]
  3. FINEP (Financiadora de Estudos e Projetos) research grant Implantacao, Modernizacao e Qualificacao de Estrutura de Pesquisada PUCRS (PUCRSINFRA) [01.11.0014-00]

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This study evaluated nucleotide hydrolysis in the plasma blood of breast cancer elderly patients, showing higher ATP and AMP hydrolysis levels in patients at the time of diagnosis compared to the control group, and significant reduction in CD73 activity after treatment. Results with a specific inhibitor showed inhibition of AMP hydrolysis.
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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