The importance of sodium/iodide symporter (NIS) for thyroid cancer management

Abstract

The thyroid gland has the ability to uptake and concentrate iodide, which is a fundamental step in thyroid hormone biosynthesis. Radioiodine has been used as a diagnostic and therapeutic tool for several years. However, the studies related to the mechanisms of iodide transport were only possible after the cloning of the gene that encodes the sodium/iodide symporter (NIS). The studies about the regulation of NIS expression and the possibility of gene therapy with the aim of transferring NIS gene to cells that normally do not express the symporter have also become possible. In the majority of hypofunctioning thyroid nodules, both benign and malignant, NIS gene expression is maintained, but NIS protein is retained in the intracellular compartment. The expression of NIS in non-thyroid tumoral cells in vivo has been possible through the transfer of NIS gene under the control of tissue-specific promoters. Apart from its therapeutic use, NIS has also been used for the localization of metastases by scintigraphy or PET-scan with 124 I. In conclusion, NIS gene cloning led to an important development in the field of thyroid pathophysiology, and has also been fundamental to extend the use of radioiodine for the management of non-thyroid tumors. A glândula tireóide tem capacidade de captar e concentrar iodeto, etapa fundamental na biossíntese dos hormônios tireóideos. O uso de iodo radioativo para fins de diagnóstico e terapia das doenças da tireóide vem sendo feito há muitos anos. Entretanto, somente após a clonagem do gene que codifica o cotransportador de sódio/iodeto (NIS) houve aumento significativo dos estudos relacionados ao mecanismo de transporte de iodeto. Os estudos sobre a regulação da expressão do NIS e a possibilidade de terapia gênica visando à transferência do gene NIS para células que normalmente não expressam esse transportador, foram também viabilizados. Na maior parte dos nódulos tireóideos hipofuncionantes, tanto benignos quanto malignos, a expressão do gene do NIS está presente, mas a proteína NIS fica retida no compartimento intracelular. A transferência do gene usando-se promotores tecido-específicos possibilitou a expressão do NIS em células tumorais não-tireóideas in vivo. Além do seu uso terapêutico, o NIS também vem sendo usado para a localização de metástases tumorais através da cintilografia ou do PET-scan usando-se 124 I. Em conclusão, a clonagem do NIS possibilitou enorme avanço na área de fisiopatologia tireóidea e foi também fundamental para estender o uso do radioiodo para tumores não tireóideos.

A new appraisal of iodine refractory thyroid cancer

“…The effectiveness of RAI therapy depends on both the radiation dose delivered to the tumor tissue and the iodine concentrating ability of the cells (Carvalho & Ferreira 2007).…”

Modeling and simulation analysis of propyl-thiouracil (PTU), an anti-thyroid drug on thyroid peroxidase (TPO), thyroid stimulating hormone receptor (TSHR), and sodium iodide (NIS) symporter based on systems biology approach

“…It has been confirmed that TSH, iodide, estrogen retinoic, cytokines, histones deacetylase inhibitors, thyroid transcription factor and thyroglobulin are keys factor that regulate the expression of NIS. Total loss of thyroid cell differentiation leads to low or zero NIS expression in thyroid cancer ultimately results in non-uptake of iodide molecule (Carvalho and Ferreira 2007). The pharmacokinetics and pharmacodynamics properties of PTU drug action given in drug bank (http://www.drugbank.ca/drugs/DB00550) support the validity of model.…”

SPET–CT in thyroid cancer: a systematic review

“…In addition to thyroid cells, NIS activity can be found in salivary glands, gastric mucosa, and lactating and non-lactating breasts [67]. Radioiodine uptake has also been identified in lacrimal glands, choroid plexus, the ciliary body of the eye, skin, placenta, and thymus [1,[67][68][69][70][71]. It is estimated that at least 22 % of radioiodine scans will have cryptic findings including benign mimics of disease [42].…”