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Extracellular ATP is Differentially Metabolized on Papillary Thyroid Carcinoma Cells Surface in Comparison to Normal Cells

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Cancer Microenvironment

Abstract

The incidence of differentiated thyroid cancer has been increasing. Nevertheless, its molecular mechanisms are not well understood. In recent years, extracellular nucleotides and nucleosides have emerged as important modulators of tumor microenvironment. Extracellular ATP is mainly hydrolyzed by NTPDase1/CD39 and NTPDase2/CD39L1, generating AMP, which is hydrolyzed by ecto-5′-nucleotidase (CD73) to adenosine, a possible promoter of tumor growth and metastasis. There are no studies evaluating the expression and functionality of these ectonucleotidases on normal or tumor-derived thyroid cells. Thus, we investigated the ability of thyroid cancer cells to hydrolyze extracellular ATP generating adenosine, and the expression of ecto-enzymes, as compared to normal cells. We found that normal thyroid derived cells presented a higher ability to hydrolyze ATP and higher mRNA levels for ENTDP1–2, when compared to papillary thyroid carcinoma (PTC) derived cells, which had a higher ability to hydrolyze AMP and expressed CD73 mRNA and protein at higher levels. In addition, adenosine induced an increase in proliferation and migration in PTC derived cells, whose effect was blocked by APCP, a non-hydrolysable ADP analogue, which is an inhibitor of CD73. Taken together, these results showed that thyroid follicular cells have a functional purinergic signaling. The higher expression of CD73 in PTC derived cells might favor the accumulation of extracellular adenosine in the tumor microenvironment, which could promote tumor progression. Therefore, as already shown for other tumors, the purinergic signaling should be considered a potential target for thyroid cancer management and treatment.

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Acknowledgements

We thank Dr. Ana Luiza Silva Maia (UFRGS-HCPA, Porto Alegre, Brazil) for providing the K1 and TPC-1 cells lines, and Dr. Denise Pires de Carvalho (UFRJ, Rio de Janeiro, Brazil) for providing Nthy-1, FRTL-5 and PCCL3 cells.

Funding

APSB was supported by a post doc fellowship from CAPES/PNPD (Programa Nacional de Pós-Doutorado); EB, MRW and TWF are recipients of research fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). This study was supported by CNPq, Novas Terapias Portadoras de Futuro (457394/2013–7); CAPES-PROBITEC (004/2012) and PROCAD (158819); ICGEB (405231/2015–6 MCTI/CNPq-ICGEB); FIPE/HCPA (N° 15–0590); and Fundação de Amparo à Pesquisa do Rio Grande do Sul (Pronex FAPERGS/CNPq 16/2551–0000473-0).

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Authors and Affiliations

  1. Departamento de Ciências Básicas da Saúde and Laboratório de Biologia Celular, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Rua Sarmento Leite, 245, Prédio III, Sala 613, Porto Alegre, RS, CEP 90050-170, Brazil

    Ana Paula Santin Bertoni, Rafael Paschoal de Campos, Elizandra Braganhol & Márcia Rosângela Wink

  2. Departamento de Farmacociências, Universidade Federal de Ciências da Saúde de Porto Alegre, Rua Sarmento Leite, 245, Prédio Principal, Sala 305, Porto Alegre, RS, CEP 90050-170, Brazil

    Marisa Tsao

  3. Programa de Pós-Graduação em Medicina: Ciências Médicas, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350/700, Porto Alegre, RS, CEP 90035-003, Brazil

    Tania Weber Furlanetto

  4. UFCSPA, Rua Sarmento Leite, 245, Prédio Principal, Sala 304, Porto Alegre, RS, CEP 90050-170, Brazil

    Márcia Rosângela Wink

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  1. Ana Paula Santin Bertoni
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  2. Rafael Paschoal de Campos
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  6. Márcia Rosângela Wink
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Correspondence to Márcia Rosângela Wink.

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Bertoni, A.P.S., de Campos, R.P., Tsao, M. et al. Extracellular ATP is Differentially Metabolized on Papillary Thyroid Carcinoma Cells Surface in Comparison to Normal Cells. Cancer Microenvironment 11, 61–70 (2018). https://doi.org/10.1007/s12307-018-0206-4

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  • DOI: https://doi.org/10.1007/s12307-018-0206-4

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