A perspective view of sodium iodide symporter research and its clinical implications

Abstract

The sodium iodide symporter (NIS) is an intrinsic plasma membrane protein that mediates active iodide transport into the thyroid gland and into several extrathyroidal tissues, in particular the lactating mammary gland. Cloning and molecular characterization of the NIS have allowed the investigation of its key role in thyroid physiology as well as its potential pathophysiological and therapeutic implications in benign and malignant thyroid diseases. Similarly, elucidating the mechanisms underlying the regulation of NIS in lactating mammary gland and breast cancer, in which more than 80% of cases express endogenous NIS, may lead to findings that have novel implications for pathophysiology and therapy. Two approaches may, in the future, pave the way to extend the use of radioiodide treatment to nonthyroidal cancer. One is based on the reinduction of endogenous NIS expression in thyroid and breast cancer by targeting the main mechanisms involving tumoral transformation and dedifferentiation. The other is based on the application of NIS as a novel cytoreductive gene therapy strategy. NIS offers the unique advantage that it can be used both as a reporter and as a therapeutic gene, so that it is possible to image, monitor, and treat the tumor with radioiodide, just as in differentiated thyroid cancer. This review summarizes the main recent findings in NIS research that have a direct impact on diagnosis and therapeutic management. European Journal of Endocrinology 155 495-512

SPECT/CT imaging of oncolytic adenovirus propagation in tumours in vivo using the Na/I symporter as a reporter gene

“…9 Another application is the combination of the imaging and therapeutic potential of the hNIS transgene. 35 Oncolytic recombinant measles viruses encoding hNIS have already been described 36,37 and used to demonstrate the concept of image-guided radiovirotherapy in a pre-clinical model of multiple myeloma. 36 Our work suggests the possibility to extend this concept to adenoviruses.…”

Human thyroid tumours, the puzzling lessons from E7 and RET/PTC3 transgenic mice

“…This can be correlated with data in the human PTC. It could be due to an increased intracellular NIS misexpression (Saito et al, 1998;Wapnir et al, 2003;Riesco-Eizaguirre and Santisteban, 2006), to conformational changes (Gérard et al, 2003) or to the non maturation of hNIS (Trouttet-Masson et al, 2004).…”

The Biology of the Sodium Iodide Symporter and its Potential for Targeted Gene Delivery

“…Delivery of exogenous hNIS in vitro resulted in more than a 120-fold increase in iodide uptake in U1240 cells infected with recombinant adenovirus expressing hNIS regulated by the CMV promoter. Intratumoural injection of Ad-CMV-hNIS into subcutaneous xenografts of U251 human gliomas resulted in a 25-fold increase in 125 I accumulation compared to the spleen or saline-injected tumours [134]. Mandell et al (1999) demonstrated in vitro and in vivo iodide accumulation in melanoma, liver, colon and ovarian carcinoma cells after retrovirus-mediated transfection with rNIS.…”

“…Rats fed on T4-supplemented diet did not show any uptake in the thyroid on subsequent 99m TcO 4 − scintigraphy. Furthermore, this correlated with a reduced level of NIS protein expression on western blot analysis [134]. Most subsequent studies have employed low-iodine diets combined with T4 supplementation (0.05-5 mg/l) for 1-2 weeks prior to radioiodide therapy [128,[150][151][152][153].…”