Sodium Iodide Symporter Is Expressed at the Preneoplastic Stages of Liver Carcinogenesis and in Human Cholangiocarcinoma

Liu, Bingkaï; Hervé, Jean-Claude; Bioulac‐Sage, Paulette; Valogne, Yannick; Roux, J.; Yılmaz, Funda; Boisgard, Raphaël; Guettier, Catherine; Calès, Paul; Tavitian, Bertrand; Samuel, Didier; Clerc, Jérôme; Bréchot, Christian; Faivre, J

doi:10.1053/j.gastro.2007.01.044

Cited by 23 publications

(37 citation statements)

References 20 publications

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“…The laboratory made R14 anti-NIS antibody revealed NIS at the basolateral plasma membrane of normal human thyroid follicles (Fig. 1A), as reported (13). NIS was strongly expressed in 12 of 15 liver metastases, displaying an intracellular localization in 5, and a mixed intracellular/plasma membrane localization in 7 tumors, without this localization being correlated with the site of the primary cancer (Fig.…”

Section: Nis Is Expressed In Liver Metastases and Invading Single Cellssupporting

confidence: 57%

“…The rabbit polyclonal anti-NIS antibody called serum R14 (13) has been purified by affinity chromatography after immobilizing a human NIS peptide (624-643) to the column. Mouse monoclonal antibody against the 625-643 C-terminal epitope of NIS (clone FP5A) was purchased from Labvision.…”

Section: Antibodiesmentioning

confidence: 99%

“…Radioiodine therapy following NIS gene transfer was shown to be efficient in nonthyroid, especially, liver cancer models. NIS is expressed in many cancers, among them cancer of the thyroid, breast, and liver (7,(11)(12)(13)(14). The role of iodide in thyroid carcinogenesis has been investigated but remains unclear (15).…”

Section: Introductionmentioning

confidence: 99%

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Iodide Transporter NIS Regulates Cancer Cell Motility and Invasiveness by Interacting with the Rho Guanine Nucleotide Exchange Factor LARG

et al. 2012

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A number of solute carrier (SLC) proteins are subject to changes in expression and activity during carcinogenesis. Whether these changes play a role in carcinogenesis is unclear, except for some nutrients and ion carriers whose deregulation ensures the necessary reprogramming of energy metabolism in cancer cells. In this study, we investigated the functional role in tumor progression of the sodium/iodide symporter (NIS; aka SLC5A5), which is upregulated and mislocalized in many human carcinomas. Notably, we found that NIS enhanced cell migration and invasion without ion transport being involved. These functions were mediated by NIS binding to leukemia-associated RhoA guanine exchange factor, a Rho guanine exchange factor that activates the small GTPase RhoA. Sequestering NIS in intracellular organelles or impairing its targeting to the cell surface (as observed in many cancers) led to a further increase in cell motility and invasiveness. In sum, our results established NIS as a carrier protein that interacts with a major cell signaling hub to facilitate tumor cell locomotion and invasion. Cancer Res; 72(21); 5505-15. Ó2012 AACR.

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Section: Nis Is Expressed In Liver Metastases and Invading Single Cellssupporting

confidence: 57%

Section: Antibodiesmentioning

confidence: 99%

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Iodide Transporter NIS Regulates Cancer Cell Motility and Invasiveness by Interacting with the Rho Guanine Nucleotide Exchange Factor LARG

et al. 2012

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“…In the recent years, it was shown in human biopsies of intrahepatic CC that this type of tumor has increased expression of sodium iodide symporter (NIS), a molecule that mediates the iodine uptake [25,26]. These results were then confirmed in in vitro studies, and a recent study in a human extrahepatic CC cell line shows that these cells also overexpress NIS [27,28].…”

Section: Molecular and Genetic Alterationsmentioning

confidence: 98%

“…NIS has a key role in metabolic radiotherapy, using iodine-131, for the treatment of thyroid tumors, being also currently under active investigation for the treatment of extrathyroidal tumors. This means that NIS overexpression opens a new possibility of treatment for CC [26,[28][29][30][31].…”

Section: Molecular and Genetic Alterationsmentioning

confidence: 99%

Cholangiocarcinoma: from molecular biology to treatment

et al. 2015

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Cholangiocarcinoma is a rare tumor originating in the bile ducts, which, according to their anatomical location, is classified as intrahepatic, extrahepatic and hilar. Nevertheless, incidence rates have increased markedly in recent decades. With respect to tumor biology, several genetic alterations correlated with resistance to chemotherapy and radiotherapy have been identified. Here, we highlight changes in KRAS and TP53 genes that are normally associated with a more aggressive phenotype. Also IL-6 and some proteins of the BCL-2 family appear to be involved in the resistance that the cholangiocarcinoma presents toward conventional therapies. With regard to diagnosis, tumor markers most commonly used are CEA and CA 19-9, and although its use isolated appears controversial, their combined value has been increasingly advocated. In imaging terms, various methods are needed, such as abdominal ultrasound, computed tomography and cholangiopancreatography. Regarding therapy, surgical modalities are the only ones that offer chance of cure; however, due to late diagnosis, most patients cannot take advantage of them. Thus, the majority of patients are directed to other therapeutic modalities like chemotherapy, which, in this context, assumes a purely palliative role. Thus, it becomes urgent to investigate new therapeutic options for this highly aggressive type of tumor.

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Endogenous expression of the sodium iodide symporter mediates uptake of iodide in murine models of colorectal carcinoma

Gaertner

Rohde

Mueller

et al. 2009

Intl Journal of Cancer

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The sodium iodide symporter (NIS) mediates iodide uptake into the thyroid. Because of this mechanism, differentiated thyroid cancer is susceptible for radioiodine therapy. Functional NIS expression in extrathyroidal tumors has been reported mainly in breast cancer. We screened colorectal tumors for NIS expression and investigated the mechanisms regulating NIS activity. Cell lines were screened for iodide uptake in vitro and NIS expression was evaluated by real-time RT-PCR, immunocytochemistry and immunoblotting. Iodide and pertechnetate uptake were evaluated in allograft tumors by biodistribution studies and scintigraphy. Tumors of transgenic mouse models for colorectal cancer harboring mutations in the oncogenes KRAS, b-catenin or the tumor-suppressor gene adenomatous-polyposis coli (APC) were screened for NIS expression by RT-PCR. In vitro, functional NIS activity was detected in murine CMT93 rectal carcinoma cells and NIS expression was verified on mRNA and protein level. Inhibition of tyrosine kinases increased iodide uptake. Inhibition of tyrosine phosphatases decreased iodide uptake. In vivo, functional NIS expression was preserved in CMT93 tumors and tumor uptake could be enhanced by treatment of mice with tyrosine kinase inhibitors. In transgenic murine models of colorectal cancer, 14% of endogenous tumors expressed elevated levels of NIS mRNA. We conclude that NIS is functionally expressed in a subset of murine colorectal tumors and its activity is regulated by tyrosine phosphorylation. Therefore, with specific tyrosine kinase inhibition, these tumors might be susceptible for radioiodine treatment. Further studies are justified to identify the specific pathways regulating NIS activity and to transfer these findings to human cell lines and tissues. ' UICCKey words: sodium iodide symporter; endogenous expression; radioiodine uptake; colorectal cancer; extrathyroidal tumorsThe sodium iodide symporter (NIS) is a glycoprotein located in the basolateral membrane of thyrocytes. It mediates the active transport of iodide from the extracellular space into the thyrocytes as the first step of thyroid hormone synthesis.1 This mechanism is used for diagnostic and therapeutic purposes in nuclear medicine. Analogous to iodide, NIS also effectively transports pertechnetate (TcO 42 ) into the intracellular space. 2 This is important for nuclear medicine applications as the widely available radionuclide 99m

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Sodium Iodide Symporter Is Expressed at the Preneoplastic Stages of Liver Carcinogenesis and in Human Cholangiocarcinoma

Cited by 23 publications

References 20 publications

Iodide Transporter NIS Regulates Cancer Cell Motility and Invasiveness by Interacting with the Rho Guanine Nucleotide Exchange Factor LARG

Iodide Transporter NIS Regulates Cancer Cell Motility and Invasiveness by Interacting with the Rho Guanine Nucleotide Exchange Factor LARG

Cholangiocarcinoma: from molecular biology to treatment

Endogenous expression of the sodium iodide symporter mediates uptake of iodide in murine models of colorectal carcinoma

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