Immunoanalysis indicates that the sodium iodide symporter is not overexpressed in intracellular compartments in thyroid and breast cancers

Peyrottes, Isabelle; Navarro, Valérie; Ondo-Méndez, Alejandro; Marcellin, Didier; Bellanger, Laurent; Marsault, Robert; Lindenthal, Sabine; Ettore, F.; Darcourt, Jacques; Pourcher, Thierry

doi:10.1530/eje-08-0505

Cited by 40 publications

(30 citation statements)

References 51 publications

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“…Although specific hNIS expression was confirmed and as expected according to the literature by Western blot (Fig. 1D) (32,33,34), the functionality of the symporter was validated by measuring the accumulation of 131 I or 99m Tc radioisotopes into the cells (Figs. 1E and 1F).…”

Section: Recombination Of Hnis and Hssr2 With Vaccinia Wyeth Strainsupporting

confidence: 82%

Enhancing Expression of Functional Human Sodium Iodide Symporter and Somatostatin Receptor in Recombinant Oncolytic Vaccinia Virus for In Vivo Imaging of Tumors

et al. 2016

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Oncolytic virus (OV) therapy has emerged as a novel tool in our therapeutic arsenals for fighting cancer. As a live biologic agent, OV has the ability to target and selectively amplify at the tumor sites. We have reported that a vaccinia-based OV (Pexa-Vec) has shown good efficacy in preclinical models and in clinical trials. To give an additional tool to clinicians to allow both treatment of the tumor and improved visualization of tumor margins, we developed new viral-based platforms with 2 specific gene reporters. Methods: We incorporated the human sodium iodide symporter (hNIS) and the human somatostatin receptor 2 (hSSR2) in the vaccinia-based OV and tested viral constructs for their abilities to track and treat tumor development in vivo. Results: Early and high-level expression of hNIS is detrimental to the recombinant virus, leading to the aggregation of hNIS protein and early cell death. Putting hNIS under a late synthetic promoter allowed a higher functional expression of the protein and much stronger 123 I or 99 Tc uptake. In vivo, the hNIS-containing virus infected and amplified in the tumor site, showing a better efficacy than the parental virus. The hNIS expression at the tumor site allowed for the imaging of viral infection and tumor regression. Similarly, hSSR2-containing OV vaccinia infected and lysed cancer cells. Conclusion: When tumor-bearing mice were given hNIS-and hSSR2-containing OV, 99 Tc and 111 In signals coalesced at the tumor, highlighting the power of using these viruses for tumor diagnosis and treatment.

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Section: Recombination Of Hnis and Hssr2 With Vaccinia Wyeth Strainsupporting

confidence: 82%

Enhancing Expression of Functional Human Sodium Iodide Symporter and Somatostatin Receptor in Recombinant Oncolytic Vaccinia Virus for In Vivo Imaging of Tumors

et al. 2016

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“…The meaning of cytoplasmic expression is still unclear. The results of Peyrotties et al (9) show that the intracellular expression of NIS relates to a non-specific signal. Rete testis invasion is thought to be a marker of aggressive behavior of testis tumors (10).…”

Section: Discussionmentioning

confidence: 97%

Sodium Iodide Symporter Protein Expression and Clinicopathological Variables in Pure Testicular Seminomas

Yazgan¹,

Ener²,

Gözalan³

et al. 2017

Cyprus J Med Sci

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BACKGROUNDTestis carcinomas cause cancer-related morbidity and mortality in adults. Radioiodine I-131 (RAI) therapy may be an alternative for the treatment. The aim of this study is to investigate the presence and localization of sodium iodide symporter (NIS) expression in pure testicular seminomas, two lymph nodes with seminoma metastasis, and two embryonal carcinomas by immunohistochemically methods. MATERIAL and METHODSThe localization of NIS expression was defined as positive according to >10% membranous staining. Cytoplasmic staining was noted as present/absent. NIS expression was compared to the invasions. RESULTSThere was no rete testis invasion in 66.7% (26/37) and epididymis invasion in 84.6% (33/37) of the cases. Lymphovascular invasion was seen in 64.1% (25/37) of the cases. There was no membranous staining in pure seminomas, but it was present in two embryonal carcinomas. Cytoplasmic staining was present in 41% (16/34) of the tumors. Cytoplasmic NIS expression was present in 72.7% (p=0.135) and 75% (p=0.6) of the rete testis and epididymis invasions, respectively. There was no statistically important relationship with the cytoplasmic expression, lymphovascular invasion, and the other parameters (p>0.05). CONCLUSIONResearch of NIS expression in pure seminomas with larger series may clear the option of RAI treatment in seminomas. Also, evidence of different expression profiles in non-seminomatous testicular tumors was determined.

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“…Other reports suggested that the NIS protein is highly regulated by post-transcriptional events that control, in particular, its subcellular localization (36,44,45). Partially glycosylated forms of NIS correspond most likely to immature proteins that are not properly processed and localized to the plasma membrane (46).…”

Section: Discussionmentioning

confidence: 99%

Propylthiouracil Increases Sodium/Iodide Symporter Gene Expression and Iodide Uptake in Rat Thyroid Cells in the Absence of TSH

Sue

Akama

Kawashima

et al. 2012

Thyroid

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Background: Propylthiouracil (PTU) and methimazole (MMI) are drugs that are widely used to treat Graves' disease. Although both exert an antithyroid effect primarily by blocking thyroid peroxidase activity, their molecular structure and other actions are different. We hypothesized that PTU and MMI may have differential effects on thyroid-specific gene expression and function. Methods: The effects of PTU and MMI on thyroid-specific gene expression and function were examined in rat thyroid FRTL-5 cells using DNA microarray, reverse transcriptase (RT)-polymerase chain reaction (PCR), real-time PCR, Western blot, immunohistochemistry, and radioiodine uptake studies. Results: DNA microarray analysis showed a marked increase in sodium/iodide symporter (NIS) gene expression after PTU treatment, whereas MMI had no effect. RT-PCR and real-time PCR analysis revealed that PTUinduced NIS mRNA levels were comparable to those elicited by thyroid-stimulating hormone (TSH). PTU increased 5¢-1880-bp and 5¢-1052-bp activity of the rat NIS promoter. While PTU treatment also increased NIS protein levels, the size of the induced protein was smaller than that induced by TSH, and the protein localized predominantly in the cytoplasm rather than the plasma membrane. Accumulation of 125 I in FRTL-5 cells was increased by PTU stimulation, but this effect was weaker than that produced by TSH. Conclusions: We found that PTU induces NIS expression and iodide uptake in rat thyroid FRTL-5 cells in the absence of TSH. Although PTU and MMI share similar antithyroid activity, their effects on other thyroid functions appear to be quite different, which could affect their therapeutic effectiveness.

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Immunoanalysis indicates that the sodium iodide symporter is not overexpressed in intracellular compartments in thyroid and breast cancers

Cited by 40 publications

References 51 publications

Enhancing Expression of Functional Human Sodium Iodide Symporter and Somatostatin Receptor in Recombinant Oncolytic Vaccinia Virus for In Vivo Imaging of Tumors

Enhancing Expression of Functional Human Sodium Iodide Symporter and Somatostatin Receptor in Recombinant Oncolytic Vaccinia Virus for In Vivo Imaging of Tumors

Sodium Iodide Symporter Protein Expression and Clinicopathological Variables in Pure Testicular Seminomas

Propylthiouracil Increases Sodium/Iodide Symporter Gene Expression and Iodide Uptake in Rat Thyroid Cells in the Absence of TSH

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