RAPID COMMUNICATION: Predominant Intracellular Overexpression of the Na+/I− Symporter (NIS) in a Large Sampling of Thyroid Cancer Cases

ABSTRACT Here we report the analysis of the Na+/I− symporter (NIS) protein expression in 57 thyroid cancer samples by immunohistochemistry with high-affinity anti-NIS Abs. As many as 70% of these samples exhibited increased NIS expression with respect to the normal surrounding thyroid tissue. Most significantly, NIS was located in these samples either in both the plasma membrane and intracellular compartments simultaneously, or exclusively in intracellular compartments. This suggests that NIS is clearly expressed or even overexpressed in most thyroid cancer cells, but malignant transformation in some of these cells interferes either with the proper targeting of NIS to the plasma membrane, or with the mechanisms that retain NIS in the plasma membrane after it has been targeted. The results further indicate that, in addition to indicating NIS expression in cases where it is absent (∼30%), improvements in 131I radioablation therapy might result from promoting targeting of NIS to the plasma membrane in the majority (∼70%) of thyroid cancers.

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Changes in Exosome Release in Thyroid Cancer Cells after Prolonged Exposure to Real Microgravity in Space

International Journal of Molecular Sciences ◽

10.3390/ijms22042132 ◽

2021 ◽

Vol 22 (4) ◽

pp. 2132

Author(s):

Petra M. Wise ◽

Paolo Neviani ◽

Stefan Riwaldt ◽

Thomas Juhl Corydon ◽

Markus Wehland ◽

...

Keyword(s):

Thyroid Cancer ◽

Protein Expression ◽

Cancer Cells ◽

Prolonged Exposure ◽

Space Station ◽

Surface Protein ◽

Surface Expression ◽

Human Thyroid ◽

Gene And Protein Expression ◽

Thyroid Cancer Cells

Space travel has always been the man’s ultimate destination. With the ability of spaceflight though, came the realization that exposure to microgravity has lasting effects on the human body. To counteract these, many studies were and are undertaken, on multiple levels. Changes in cell growth, gene, and protein expression have been described in different models on Earth and in space. Extracellular vesicles, and in particular exosomes, are important cell-cell communicators, being secreted from almost all the cells and therefore, are a perfect target to further investigate the underlying reasons of the organism’s adaptations to microgravity. Here, we studied supernatants harvested from the CellBox-1 experiment, which featured human thyroid cancer cells flown to the International Space Station during the SpaceX CRS-3 cargo mission. The initial results show differences in the number of secreted exosomes, as well as in the distribution of subpopulations in regards to their surface protein expression. Notably, alteration of their population regarding the tetraspanin surface expression was observed. This is a promising step into a new area of microgravity research and will potentially lead to the discovery of new biomarkers and pathways of cellular cross-talk.

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Exosomal ANXA1 derived from thyroid cancer cells is associated with malignant transformation of human thyroid follicular epithelial cells by promoting cell proliferation

International Journal of Oncology ◽

10.3892/ijo.2021.5284 ◽

2021 ◽

Vol 59 (6) ◽

Author(s):

Qingchun Li ◽

Wei Liu ◽

Zhenglin Wang ◽

Cong Wang ◽

Zhilong Ai

Keyword(s):

Cell Proliferation ◽

Thyroid Cancer ◽

Epithelial Cells ◽

Cancer Cells ◽

Malignant Transformation ◽

Human Thyroid ◽

Thyroid Cancer Cells ◽

Follicular Epithelial

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Inhibition of gap junction transfer sensitizes thyroid cancer cells to anoikis

Endocrine Related Cancer ◽

10.1530/erc-10-0289 ◽

2011 ◽

Vol 18 (5) ◽

pp. 613-626 ◽

Cited By ~ 16

Author(s):

Kirk Jensen ◽

Aneeta Patel ◽

Joanna Klubo-Gwiezdzinska ◽

Andrew Bauer ◽

Vasyl Vasko

Keyword(s):

Thyroid Cancer ◽

Gap Junction ◽

Cancer Cells ◽

Cancer Cell ◽

Thyroid Tissue ◽

Human Thyroid ◽

Thyroid Cancer Cell ◽

Gap Junctional ◽

Thyroid Cancer Cells

Resistance to anoikis (matrix deprivation-induced apoptosis) is a critical component of the metastatic cascade. Molecular mechanisms underlying resistance to anoikis have not been reported in thyroid cancer cells. For an in vitro model of anoikis, we cultured follicular, papillary, and anaplastic thyroid cancer cell lines on poly-HEMA-treated low-adherent plates. We also performed immunohistochemical analysis of human cancer cells that had infiltrated blood and/or lymphatic vessels. Matrix deprivation was associated with establishment of contacts between floating thyroid cancer cells and formation of multi-cellular spheroids. This process was associated with activation of gap junctional transfer. Increased expression of the gap junction molecule Connexin43 was found in papillary and anaplastic cancer cells forming spheroids. All non-adherent cancer cells showed a lower proliferation rate compared with adherent cells but were more resistant to serum deprivation. AKT was constitutively activated in cancer cells forming spheroids. Inhibition of gap junctional transfer through Connexin43 silencing, or by treatment with the gap junction disruptor carbenoxolone, resulted in loss of pAKT and induction of apoptosis in a cell-type-specific manner. In human thyroid tissue, cancer cells that had infiltrated blood vessels showed morphological similarity to cancer cells forming spheroids in vitro. Intra-vascular cancer cells demonstrated prominent AKT activation in papillary and follicular cancers. Increased Connexin43 immunoreactivity was observed only in intra-vascular papillary cancer cells. Our data demonstrate that establishment of inter-cellular communication contributes to thyroid cancer cell resistance to anoikis. These findings suggest that disruption of gap junctional transfer could represent a potential therapeutic strategy for prevention of metastases.

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High mobility group A1 protein expression reduces the sensitivity of colon and thyroid cancer cells to antineoplastic drugs

BMC Cancer ◽

10.1186/1471-2407-14-851 ◽

2014 ◽

Vol 14 (1) ◽

Cited By ~ 26

Author(s):

Daniela D’Angelo ◽

Paula Mussnich ◽

Roberta Rosa ◽

Roberto Bianco ◽

Giampaolo Tortora ◽

...

Keyword(s):

Thyroid Cancer ◽

Protein Expression ◽

Cancer Cells ◽

High Mobility ◽

High Mobility Group ◽

Antineoplastic Drugs ◽

Thyroid Cancer Cells

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Id1 Gene Expression Is Up-Regulated in Hyperplastic and Neoplastic Thyroid Tissue and Regulates Growth and Differentiation in Thyroid Cancer Cells

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2004-1234 ◽

2004 ◽

Vol 89 (12) ◽

pp. 6105-6111 ◽

Cited By ~ 22

Author(s):

Electron Kebebew ◽

Miao Peng ◽

Patrick A. Treseler ◽

Orlo H. Clark ◽

Quan-Yang Duh ◽

...

Keyword(s):

Gene Expression ◽

Thyroid Cancer ◽

Cancer Cells ◽

Thyroid Tissue ◽

Thyroid Cancer Cells

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Quercetin-Induced Cell Death in Human Papillary Thyroid Cancer (B-CPAP) Cells

Journal of Thyroid Research ◽

10.1155/2016/9843675 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 13

Author(s):

Ergül Mutlu Altundağ ◽

Tolga Kasacı ◽

Ayşe Mine Yılmaz ◽

Betül Karademir ◽

Semra Koçtürk ◽

...

Keyword(s):

Cell Death ◽

Thyroid Cancer ◽

Protein Expression ◽

Cancer Cells ◽

Papillary Thyroid Cancer ◽

Annexin V ◽

Proteasome Activity ◽

Papillary Thyroid ◽

Candidate Drug ◽

Thyroid Cancer Cells

In this study, we have investigated the antiproliferative effect of quercetin on human papillary thyroid cancer cells and determined the apoptotic mechanisms underlying its actions. We have used different concentrations of quercetin to induce apoptosis and measured cell viability. Apoptosis and cell cycle analysis was determined by flow cytometry using Annexin V and propidium iodide. Finally, we have measured changes in caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) protein expression levels as hallmarks of apoptosis and Hsp90 protein expression level as a marker of proteasome activity in treated and control cells. Quercetin treatment of human papillary thyroid cancer cells resulted in decreased cell proliferation and increased rate of apoptosis by caspase activation. Furthermore, it was demonstrated that quercetin induces cancer cell apoptosis by downregulating the levels of Hsp90. In conclusion, we have shown that quercetin induces downregulation of Hsp90 expression that may be involved in the decrease of chymotrypsin-like proteasome activity which, in order, induces inhibition of growth and causes cell death in thyroid cancer cells. Thus, quercetin appears to be a promising candidate drug for Hsp90 downregulation and apoptosis of thyroid cancer cells.

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PTEN regulates plasma membrane expression of glucose transporter 1 and glucose uptake in thyroid cancer cells

Journal of Molecular Endocrinology ◽

10.1530/jme-14-0118 ◽

2014 ◽

Vol 53 (2) ◽

pp. 247-258 ◽

Cited By ~ 19

Author(s):

Federica Morani ◽

Suratchanee Phadngam ◽

Carlo Follo ◽

Rossella Titone ◽

Gianluca Aimaretti ◽

...

Keyword(s):

Plasma Membrane ◽

Thyroid Cancer ◽

Glucose Uptake ◽

Cancer Cells ◽

Fdg Pet ◽

Glucose Transporter ◽

Loss Of Function ◽

Membrane Expression ◽

Glucose Transporter 1 ◽

Thyroid Cancer Cells

Glucose represents an important source of energy for the cells. Proliferating cancer cells consume elevated quantity of glucose, which is converted into lactate regardless of the presence of oxygen. This phenomenon, known as the Warburg effect, has been proven to be useful for imaging metabolically active tumours in cancer patients by 18F-fluorodeoxyglucose positron emission tomography (FDG–PET). Glucose is internalised in the cells by glucose transporters (GLUTs) belonging to the GLUT family. GLUT1 (SLC2A1) is the most prevalent isoform in more aggressive and less differentiated thyroid cancer histotypes. In a previous work, we found that loss of expression of PTEN was associated with increased expression of GLUT1 on the plasma membrane (PM) and probability of detecting thyroid incidentalomas by FDG–PET. Herein, we investigated the molecular pathways that govern the expression of GLUT1 on the PM and the glucose uptake in WRO (expressing WT PTEN) and FTC133 (PTEN null) follicular thyroid cancer cells cultured under glucose-depleted conditions. The membrane expression of GLUT1 was enhanced in glucose-deprived cells. Through genetic manipulations of PTEN expression, we could demonstrate that the lack of this oncosuppressor has a dominant effect on the membrane expression of GLUT1 and glucose uptake. We conclude that loss of function of PTEN increases the probability of cancer detection by FDG–PET or other glucose-based imaging diagnosis.

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Sphingosine 1-phosphate and human ether-a′-go-go-related gene potassium channels modulate migration in human anaplastic thyroid cancer cells

Endocrine Related Cancer ◽

10.1530/erc-12-0092 ◽

2012 ◽

Vol 19 (5) ◽

pp. 667-680 ◽

Cited By ~ 8

Author(s):

Muhammad Yasir Asghar ◽

Tero Viitanen ◽

Kati Kemppainen ◽

Kid Törnquist

Keyword(s):

Thyroid Cancer ◽

Potassium Channels ◽

Protein Expression ◽

Cancer Cells ◽

Kinase Inhibitor ◽

Anaplastic Thyroid Cancer ◽

Human Thyroid ◽

Related Gene ◽

Sphingosine 1 Phosphate ◽

Thyroid Cancer Cells

Anaplastic thyroid cancer (ATC) is the most aggressive form of human thyroid cancer, lacking any effective treatment. Sphingosine 1-phosphate (S1P) receptors and human ether-a′-go-go-related gene (HERG (KCNH2)) potassium channels are important modulators of cell migration. In this study, we have shown that the S1P1–3 receptors are expressed in C643 and THJ-16T human ATC cell lines, both at mRNA and protein level. S1P inhibited migration of these cells and of follicular FTC-133 thyroid cancer cells. Using the S1P1,3 inhibitor VPC-23019, the S1P2 inhibitor JTE-013, and the S1P2 receptor siRNA, we showed that the effect was mediated through S1P2. Treatment of the cells with the Rho inhibitor C3 transferase abolished the effect of S1P on migration. S1P attenuated Rac activity, and inhibiting Rac decreased migration. Sphingosine kinase inhibitor enhanced basal migration of cells, and addition of exogenous S1P inhibited migration. C643 cells expressed a nonconducting HERG protein, and S1P decreased HERG protein expression. The HERG blocker E-4031 decreased migration. Interestingly, downregulating HERG protein with siRNA decreased the basal migration. In experiments using HEK cells overexpressing HERG, we showed that S1P decreased channel protein expression and current and that S1P attenuated migration of the cells. We conclude that S1P attenuates migration of C643 ATC cells by activating S1P2 and the Rho pathway. The attenuated migration is also, in part, dependent on a S1P-induced decrease of HERG protein.

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