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

2007 ◽  
Vol 51 (5) ◽  
pp. 672-682 ◽  
Author(s):  
Denise P. Carvalho ◽  
Andrea C.F. Ferreira
Keyword(s):  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Therapeutic Tool ◽  
Iodide Transport ◽  
Cancer Management ◽  
Thyroid Hormone Biosynthesis ◽  
Nis Gene ◽  
Hormone Biosynthesis ◽  
Tumoral Cells

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 124I. 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.

scholarly journals Rapid regulation of thyroid sodium–iodide symporter activity by thyrotrophin and iodine

2005 ◽  
Vol 184 (1) ◽  
pp. 69-76 ◽  
Author(s):  
Andrea C F Ferreira ◽  
Lívia P Lima ◽  
Renata L Araújo ◽  
Glaucia Müller ◽  
Renata P Rocha ◽  
...  
Keyword(s):  
Sodium Iodide ◽  
Iodine Content ◽  
Concomitant Administration ◽  
High Serum ◽  
Sodium Iodide Symporter ◽  
Physiological Control ◽  
Iodide Uptake ◽  
Thyroid Hormone Biosynthesis ◽  
Serum Tsh

Transport of iodide into thyrocytes, a fundamental step in thyroid hormone biosynthesis, depends on the presence of the sodium–iodide symporter (NIS). The importance of the NIS for diagnosis and treatment of diseases has raised several questions about its physiological control. The goal of this study was to evaluate the influence of thyroid iodine content on NIS regulation by thyrotrophin (TSH) in vivo. We showed that 15-min thyroid radioiodine uptake can be a reliable measurement of NIS activity in vivo. The effect of TSH on the NIS was evaluated in rats treated with 1-methyl-2-mercaptoimidazole (MMI; hypothyroid with high serum TSH concentrations) for 21 days, and after 1 (R1d), 2 (R2d), or 5 (R5d) days of withdrawal of MMI. NIS activity was significantly greater in both MMI and R1d rats. In R2d and R5d groups, thyroid iodide uptake returned to normal values, despite continuing high serum TSH, possibly as a result of the re-establishment of iodine organification after withdrawal of MMI. Excess iodine (0.05% NaI for 6 days) promoted a significant reduction in thyroid radioiodide uptake, an effect that was blocked by concomitant administration of MMI, confirming previous findings that iodine organification is essential for the iodide transport blockade seen during iodine overload. Therefore, our data show that modulation of the thyroid NIS by TSH depends primarily on thyroid iodine content and, further, that the regulation of NIS activity is rapid.

scholarly journals Sodium Iodide Symporter (NIS)-Mediated Radionuclide (131I, 188Re) Therapy of Liver Cancer After Transcriptionally Targeted Intratumoral in Vivo NIS Gene Delivery

2011 ◽  
Vol 22 (11) ◽  
pp. 1403-1412 ◽  
Author(s):  
Kathrin Klutz ◽  
Michael J. Willhauck ◽  
Nathalie Wunderlich ◽  
Christian Zach ◽  
Martina Anton ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Liver Cancer ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Nis Gene

scholarly journals A Homozygous Missense Mutation of the Sodium/Iodide Symporter Gene Causing Iodide Transport Defect1

1997 ◽  
Vol 82 (12) ◽  
pp. 3966-3971
Author(s):  
Akira Matsuda ◽  
Shinji Kosugi
Keyword(s):  
Missense Mutation ◽  
Ribonucleic Acid ◽  
Sodium Iodide ◽  
Northern Analysis ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Complementary Dna ◽  
Homozygous Missense Mutation ◽  
Iodide Transport ◽  
Nis Gene

Iodide transport defect is a disorder characterized by an inability of the thyroid to maintain an iodide concentration difference between the plasma and the thyroid. The recent cloning of the sodium/iodide symporter (NIS) gene enabled us to characterize the NIS gene in this disorder. We identified a homozygous missense mutation of A→C at nucleotide +1060 in NIS complementary DNA in a male patient who was born from consanguineous marriage, had a huge goiter, and lacked the ability to accumulate iodide but was essentially euthyroid. The mutation results in an amino acid replacement of Thr354→Pro in the middle of the ninth transmembrane domain. COS-7 cells transfected with the mutant NIS complementary DNA showed markedly decreased iodide uptake, confirming that this mutation was the direct cause of the disorder in the patient. Northern analysis of thyroid ribonucleic acid revealed that NIS messenger ribonucleic acid level was markedly increased (>100-fold) compared with that in the normal thyroid, suggesting possible compensation by overexpression.

scholarly journals Na+ coordination at the Na2 site of the Na+/I− symporter

2016 ◽  
Vol 113 (37) ◽  
pp. E5379-E5388 ◽  
Author(s):  
Giuseppe Ferrandino ◽  
Juan Pablo Nicola ◽  
Yuly E. Sánchez ◽  
Ignacia Echeverria ◽  
Yunlong Liu ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Binding Sites ◽  
Sodium Iodide ◽  
The Other ◽  
Similar Function ◽  
Sodium Iodide Symporter ◽  
Whole Cells ◽  
Thyroid Hormone Biosynthesis ◽  
Hormone Biosynthesis ◽  
Medical Relevance

The sodium/iodide symporter (NIS) mediates active I− transport in the thyroid—the first step in thyroid hormone biosynthesis—with a 2 Na+: 1 I− stoichiometry. The two Na+ binding sites (Na1 and Na2) and the I− binding site interact allosterically: when Na+ binds to a Na+ site, the affinity of NIS for the other Na+ and for I− increases significantly. In all Na+-dependent transporters with the same fold as NIS, the side chains of two residues, S353 and T354 (NIS numbering), were identified as the Na+ ligands at Na2. To understand the cooperativity between the substrates, we investigated the coordination at the Na2 site. We determined that four other residues—S66, D191, Q194, and Q263—are also involved in Na+ coordination at this site. Experiments in whole cells demonstrated that these four residues participate in transport by NIS: mutations at these positions result in proteins that, although expressed at the plasma membrane, transport little or no I−. These residues are conserved throughout the entire SLC5 family, to which NIS belongs, suggesting that they serve a similar function in the other transporters. Our findings also suggest that the increase in affinity that each site displays when an ion binds to another site may result from changes in the dynamics of the transporter. These mechanistic insights deepen our understanding not only of NIS but also of other transporters, including many that, like NIS, are of great medical relevance.

Re-visiting autoimmunity to sodium-iodide symporter and pendrin in thyroid disease

2020 ◽  
Vol 183 (6) ◽  
pp. 571-580
Author(s):  
Anna-Maria Eleftheriadou ◽  
Sebastian Mehl ◽  
Kostja Renko ◽  
Rega H Kasim ◽  
Jasmin-Annabelle Schaefer ◽  
...  
Keyword(s):  
Thyroid Disease ◽  
Sodium Iodide ◽  
Matrix Effects ◽  
Serum Zinc ◽  
Study Groups ◽  
Firefly Luciferase ◽  
Hek293 Cells ◽  
Sodium Iodide Symporter ◽  
Iodide Transport ◽  
Thyroid Hormone Biosynthesis

Objective Iodide transport across thyrocytes constitutes a critical step for thyroid hormone biosynthesis, mediated mainly by the basolateral sodium-iodide-symporter (NIS (SLC5A5)) and the apical anion exchanger pendrin (PDS (SLC26A4)). Both transmembrane proteins have been described as autoantigens in thyroid disease, yet the reports on autoantibody (aAb) prevalence and diagnostic usefulness are conflicting. Reasons for the inconclusive findings may be small study groups and principle differences in the technologies used. Design We decided to re-evaluate this important issue by establishing novel non-radioactive tests using full-length antigens and comparable protocols, and analyzing a large cohort of thyroid patients (n = 323) and control samples (n = 400). Methods NIS and PDS were recombinantly expressed as fusion protein with firefly luciferase (Luc). Stably transfected HEK293 cells were used as reproducible source of the autoantigens. Results Recombinant NIS-Luc showed iodide transport activity, indicating successful expression and correct processing. Commercial antibodies yielded dose-dependent responses in the newly established assays. Reproducibility of assay signals from patient sera was verified with respect to linearity, stability and absence of matrix effects. Prevalence of PDS-aAb was similar in thyroid patients and controls (7.7% vs 5.0%). NIS-aAb were more prevalent in patients than controls (7.7% vs 1.8%), especially in Graves’ Disease (12.3%). Neither NIS-aAb nor PDS-aAb concentrations were related to TPO-aAb or TSH-receptor-aAb concentrations, or to serum zinc or selenium status. Conclusions Our data highlight a potential relevance of autoimmunity against NIS for thyroid disease, whereas an assessment of PDS-aAb in thyroid patients seems not to be of diagnostic value (yet).

scholarly journals In vivo Radioiodide Imaging and Treatment of Breast Cancer Xenografts after MUC1-Driven Expression of the Sodium Iodide Symporter

2005 ◽  
Vol 11 (4) ◽  
pp. 1483-1489 ◽  
Author(s):  
Roisin M. Dwyer ◽  
Elizabeth R. Bergert ◽  
Michael K. O'Connor ◽  
Sandra J. Gendler ◽  
John C. Morris
Keyword(s):  
Breast Cancer ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Breast Cancer Xenografts

scholarly journals In vivo long-term imaging and radioiodine therapy by sodium-iodide symporter gene expression using a lentiviral system containing ubiquitin C promoter

2007 ◽  
Vol 6 (7) ◽  
pp. 1130-1135 ◽  
Author(s):  
Hyun Joo Kim ◽  
Yong Hyun Jeon ◽  
Joo Hyun Kang ◽  
Yong Jin Lee ◽  
Kwang Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sodium Iodide ◽  
Radioiodine Therapy ◽  
Sodium Iodide Symporter

scholarly journals The Sodium-Iodide Symporter NIS and Pendrin in Iodide Homeostasis of the Thyroid

Endocrinology ◽  
2009 ◽  
Vol 150 (3) ◽  
pp. 1084-1090 ◽  
Author(s):  
Aigerim Bizhanova ◽  
Peter Kopp
Keyword(s):  
Autosomal Recessive ◽  
Sodium Iodide ◽  
Basolateral Membrane ◽  
Sensorineural Deafness ◽  
Sodium Iodide Symporter ◽  
Pendred Syndrome ◽  
Iodide Uptake ◽  
Anion Transporter ◽  
Thyroid Hormone Biosynthesis ◽  
Biallelic Mutations

Thyroid hormones are essential for normal development and metabolism. Thyroid hormone biosynthesis requires iodide uptake into the thyrocytes and efflux into the follicular lumen, where it is organified on selected tyrosyls of thyroglobulin. Uptake of iodide into the thyrocytes is mediated by an intrinsic membrane glycoprotein, the sodium-iodide symporter (NIS), which actively cotransports two sodium cations per each iodide anion. NIS-mediated transport of iodide is driven by the electrochemical sodium gradient generated by the Na+/K+-ATPase. NIS is expressed in the thyroid, the salivary glands, gastric mucosa, and the lactating mammary gland. TSH and iodide regulate iodide accumulation by modulating NIS activity via transcriptional and posttranscriptional mechanisms. Biallelic mutations in the NIS gene lead to a congenital iodide transport defect, an autosomal recessive condition characterized by hypothyroidism, goiter, low thyroid iodide uptake, and a low saliva/plasma iodide ratio. Pendrin is an anion transporter that is predominantly expressed in the inner ear, the thyroid, and the kidney. Biallelic mutations in the SLC26A4 gene lead to Pendred syndrome, an autosomal recessive disorder characterized by sensorineural deafness, goiter, and impaired iodide organification. In thyroid follicular cells, pendrin is expressed at the apical membrane. Functional in vitro data and the impaired iodide organification observed in patients with Pendred syndrome support a role of pendrin as an apical iodide transporter. This review shows how the sodium-iodide symporter mediates the active transport of iodide at the basolateral membrane of thyrocytes and discusses biallelic mutations in NIS and the effects of pendrin.

scholarly journals Evaluation of Lentiviral-Mediated Expression of Sodium Iodide Symporter in Anaplastic Thyroid Cancer and the Efficacy of In Vivo Imaging and Therapy

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Chien-Chih Ke ◽  
Ya-Ju Hsieh ◽  
Luen Hwu ◽  
Fu-Hui Wang ◽  
Fu-Du Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sodium Iodide ◽  
Cell Function ◽  
Tumor Imaging ◽  
Promising Result ◽  
Anaplastic Thyroid Cancer ◽  
Anaplastic Thyroid Carcinoma ◽  
Sodium Iodide Symporter

Anaplastic thyroid carcinoma (ATC) is one of the most deadly cancers. With intensive multimodalities of treatment, the survival remains low. ATC is not sensitive to131I therapy due to loss of sodium iodide symporter (NIS) gene expression. We have previously generated a stable human NIS-expressing ATC cell line, ARO, and the ability of iodide accumulation was restored. To make NIS-mediated gene therapy more applicable, this study aimed to establish a lentiviral system for transferring hNIS gene to cells and to evaluate the efficacy of in vitro and in vivo radioiodide accumulation for imaging and therapy. Lentivirus containing hNIS cDNA were produced to transduce ARO cells which do not concentrate iodide. Gene expression, cell function, radioiodide imaging and treatment were evaluated in vitro and in vivo. Results showed that the transduced cells were restored to express hNIS and accumulated higher amount of radioiodide than parental cells. Therapeutic dose of131I effectively inhibited the tumor growth derived from transduced cells as compared to saline-treated mice. Our results suggest that the lentiviral system efficiently transferred and expressed hNIS gene in ATC cells. The transduced cells showed a promising result of tumor imaging and therapy.

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