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PDE5 expression in human thyroid tumors and effects of PDE5 inhibitors on growth and migration of cancer cells

Endocrine volume 50, pages 434–441 (2015)Cite this article

Abstract

Recent studies have revealed in normal thyroid tissue the presence of the transcript of several phosphodiesterases (PDEs), enzymes responsible for the hydrolysis of cyclic nucleotides. In this work, we analyzed the expression of PDE5 in a series of human papillary thyroid carcinomas (PTCs) presenting or not BRAF V600E mutation and classified according to ATA risk criteria. Furthermore, we tested the effects of two PDE5 inhibitors (sildenafil, tadalafil) against human thyroid cancer cells. PDE5 gene and protein expression were analyzed in two different cohorts of PTCs by real-time PCR using a TaqMan micro-fluid card system and Western blot. MTT and migration assay were used to evaluate the effects of PDE5 inhibitors on proliferation and migration of TPC-1, BCPAP, and 8505C cells. In a first series of 36 PTCs, we found higher expression levels of PDE5A in tumors versus non-tumor (normal) tissues. PTCs with BRAF mutation showed higher levels of mRNA compared with those without mutation. No significant differences were detected between subgroups with low and intermediate ATA risk. Upregulation of PDE5 was also detected in tumor tissue proteins. Similar results were obtained analyzing the second cohort of 50 PTCs. Moreover, all tumor tissues with high PDE5 levels showed reduction of Thyroglobulin, TSH receptor, Thyroperoxidase, and NIS transcripts. In thyroid cancer cells in vitro, sildenafil and tadalafil determined a reduction of proliferation and cellular migration. Our findings demonstrate for the first time an overexpression of PDE5 in PTCs, and the ability of PDE5 inhibitors to block the proliferation of thyroid cancer cells in culture, therefore, suggesting that specific inhibition of PDE5 may be proposed for the treatment of these tumors.

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Acknowledgments

This work was supported by Fondazione Umberto Di Mario.

Funding

This work is funded by grant to MC (MIUR: Grant RBFR12FI27_003).

Conflict of interest

The authors declare that they have no conflict of interest.

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    Authors and Affiliations

    1. Department of Internal Medicine and Medical Specialties, University of Rome “Sapienza”, 00161, Rome, Italy

      Marialuisa Sponziello, Antonella Verrienti, Francesca Rosignolo, Valeria Pecce, Cosimo Durante & Sebastiano Filetti

    2. Department of Health Sciences, University of Catanzaro “Magna Graecia”, Campus “S. Venuta”, Viale Europa, 88100, Catanzaro, Italy

      Roberta Francesca De Rose, Valentina Maggisano, Stefania Bulotta, Diego Russo & Marilena Celano

    3. Institute of Medical Genetics, University Hospital “S. Maria della Misericordia”, 33100, Udine, Italy

      Giuseppe Damante

    4. Department of Surgical Sciences, University of Rome “Sapienza”, 00161, Rome, Italy

      Laura Giacomelli

    5. Department of Radiological, Oncological and Pathological Sciences, University of Rome “Sapienza”, 00161, Rome, Italy

      Cira Rosaria Tiziana Di Gioia

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    1. Marialuisa Sponziello
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    2. Antonella Verrienti
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    Correspondence to Diego Russo.

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    Marialuisa Sponziello and Antonella Verrienti have contributed equally to this work.

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    Sponziello, M., Verrienti, A., Rosignolo, F. et al. PDE5 expression in human thyroid tumors and effects of PDE5 inhibitors on growth and migration of cancer cells. Endocrine 50, 434–441 (2015). https://doi.org/10.1007/s12020-015-0586-x

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