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Regulation of the sodium/iodide symporter by retinoids--a review
1Medical Clinic, Department of Molecular Internal Medicine, University of Würzburg, Germany. kfg.zell@mail.uni-wuerzburg.de
Abstract:
Decrease or loss of iodide uptake, due to impaired expression and/or function of the sodium/iodide-symporter (NIS), is a major obstacle to the treatment of advanced thyroid carcinomas by radioiodide therapy. Several approaches are being evaluated to optimise or restore sufficient iodide transport in those cases, among them retinoid therapy. Retinoids with their growth-inhibiting and differentiation-inducing properties have been repeatedly used for treatment and chemoprevention of various cancers. In thyroid carcinoma cell lines they trigger changes in gene expression that may be interpreted as partial redifferentiation. Especially, they stimulate NIS mRNA expression and iodide uptake in human follicular thyroid carcinoma cells. Moreover, they also increase NIS expression and function in human mammary tumour cells. In a clinical pilot study to evaluate the feasibility of retinoid redifferentiation in the case of otherwise untreatable thyroid cancers, 21 of 50 patients showed an increase of radioiodide uptake after 5 weeks. This indicates that increasing NIS activity and radioiodide uptake by retinoic acid redifferentiation may be a therapeutic alternative for thyroid cancers refractory to other therapeutic modalities and probably also for mammary cancer.
Insights
Retinoid therapy can restore radioiodide uptake in advanced thyroid cancers by increasing sodium/iodide-symporter (NIS) expression. This approach offers a potential treatment for radioiodide-refractory thyroid and mammary tumors.
Area of Science:
- Oncology
- Molecular Endocrinology
Background:
- Radioiodide therapy is limited in advanced thyroid cancers by decreased sodium/iodide-symporter (NIS) expression or function.
- Retinoids are known for their anti-cancer properties, including growth inhibition and differentiation induction.
- Retinoids have shown potential in partially redifferentiating thyroid carcinoma cells and increasing NIS expression.
Purpose of the Study:
- To evaluate the feasibility of retinoid therapy to restore radioiodide uptake in advanced thyroid cancers.
- To investigate the effect of retinoids on sodium/iodide-symporter (NIS) expression and function in thyroid and mammary tumor cells.
Main Methods:
- Treatment of thyroid carcinoma cell lines with retinoids to assess changes in gene expression and iodide uptake.
- Clinical pilot study administering retinoid therapy to patients with advanced, untreatable thyroid cancers.
- Monitoring radioiodide uptake in patients before and after retinoid treatment.
Main Results:
- Retinoids stimulated NIS mRNA expression and iodide uptake in human follicular thyroid carcinoma cells.
- Retinoids also increased NIS expression and function in human mammary tumor cells.
- In a clinical pilot study, 21 out of 50 patients demonstrated increased radioiodide uptake after 5 weeks of retinoid therapy.
Conclusions:
- Retinoid redifferentiation can increase sodium/iodide-symporter (NIS) activity and radioiodide uptake.
- This approach represents a potential therapeutic alternative for thyroid cancers resistant to conventional treatments.
- Retinoid therapy may also be beneficial for mammary cancers with impaired iodide uptake.