Sodium iodide symporter (NIS) in extrathyroidal malignancies: focus on breast and urological cancer.

Salvatore Micali,Giampaolo Bianchi,Stefania Bulotta,Sebastiano Filetti,Diego Russo,Angelo Territo,Michele Navarra,Cinzia Puppin,Giuseppe Damante

doi:10.1186/1471-2407-14-303

Salvatore Micali, Giampaolo Bianchi + Show 7 more

Open Access

https://doi.org/10.1186/1471-2407-14-303

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Abstract

BackgroundExpression and function of sodium iodide symporter (NIS) is requisite for efficient iodide transport in thyrocytes, and its presence in cancer cells allows the use of radioiodine as a diagnostic and therapeutic tool in thyroid neoplasia. Discovery of NIS expression in extrathyroidal tissues, including transformed cells, has opened a novel field of research regarding NIS-expressing extrathyroidal neoplasia. Indeed, expression of NIS may be used as a biomarker for diagnostic, prognostic, and therapeutic purposes. Moreover, stimulation of endogenous NIS expression may permit the radioiodine treatment of extrathyroidal lesions by concentrating this radioisotope.ResultsThis review describes recent findings in NIS research in extrathyroidal malignancies, focusing on breast and urological cancer, emphasizing the most relevant developments that may have clinical impact.ConclusionsGiven the recent progress in the study of NIS regulation as molecular basis for new therapeutic approaches in extrathyroidal cancers, particular attention is given to studies regarding the relationship between NIS and clinical-pathological aspects of the tumors and the regulation of NIS expression in the experimental models.

Highlights

The sodium iodide symporter (NIS) is a glycosylated protein with 13 trans-membrane domains, belonging to the solute carrier family [1,2] (Figure 1)
Sodium iodide symporter (NIS) activity is necessary to provide the iodide concentration gradient inside thyroid cells, used for the synthesis of thyroid hormones in a multistep process requiring the action of pendrin, thyroid peroxidase (TPO), dual oxidase-2, and thyroglobulin
In a larger study including a series of 107 testicular tumors, we have recently demonstrated that NIS is expressed in the plasma membrane of the large majority of seminomas and embryonal carcinomas of human testis, while it is absent in Leydig cell cancers [75]

Summary

Conclusions

Given the recent progress in the study of NIS regulation as molecular basis for new therapeutic approaches in extrathyroidal cancers, particular attention is given to studies regarding the relationship between NIS and clinical-pathological aspects of the tumors and the regulation of NIS expression in the experimental models.

Introduction

15. Wright EM

24. Brown-Grant K

49. Gendler SJ