scholarly journals Stromal Interaction Molecule 1 (STIM1) Knock-down Attenuates Migration and Proliferation and Enhances the Expression of Thyroid Specific Proteins in Human Follicular Thyroid Cancer Cells.

2021 ◽  
Author(s):  
Muhammad Yasir Asghar ◽  
Taru Lassila ◽  
Ilkka Paatero ◽  
Van Dien Nguyen ◽  
Pauliina Kronqvist ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Stimulating Hormone ◽  
Cancer Tissue ◽  
Thyroid Cells ◽  
Knock Down ◽  
Stromal Interaction Molecule 1 ◽  
Store Operated Calcium Entry ◽  
Specific Proteins ◽  
Thyroid Cancer Cell Lines ◽  
And Function

Abstract Stromal interaction molecule 1 (STIM1) and the ORAI1 calcium channel mediate store-operated calcium entry (SOCE) and regulate a multitude of cellular functions. The identity and function of these proteins in thyroid cancer remained elusive. We show that STIM1 and ORAI1 expression is elevated in thyroid cancer cell lines, compared with primary thyroid cells. Knock-down of STIM1 or ORAI1 attenuated SOCE, reduced migration, and expression of promigratory sphingosine 1-phosphate (S1P) and vascular endothelial growth factor-2 (VEGFR2) receptors in thyroid cancer ML-1 cells. Cell proliferation was attenuated in these knock-down cells due to increased G1 phase of the cell cycle and enhanced expression of cyclin-dependent kinase inhibitory proteins p21 and p27. STIM1 protein was upregulated in thyroid cancer tissue, compared with normal tissue. Downregulation of STIM1 restored expression of thyroid stimulating hormone receptor (TSHR), thyroid specific proteins and increased iodine uptake. STIM1 knockdown ML-1 cells were more susceptible to chemotherapeutic drugs, and significantly reduced tumor growth in Zebrafish. Furthermore, STIM1-siRNA-loaded mesoporous polydopamine nanoparticles attenuated migration and proliferation of ML-1 cells. Taken together, our data suggest that STIM1 is a potential diagnostic and therapeutic target for treatment of thyroid cancer.

scholarly journals Stromal interaction molecule 1 (STIM1) knock down attenuates invasion and proliferation and enhances the expression of thyroid-specific proteins in human follicular thyroid cancer cells

2021 ◽  
Author(s):  
Muhammad Yasir Asghar ◽  
Taru Lassila ◽  
Ilkka Paatero ◽  
Van Dien Nguyen ◽  
Pauliina Kronqvist ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Stimulating Hormone ◽  
Cancer Tissue ◽  
Thyroid Cells ◽  
Knock Down ◽  
Stromal Interaction Molecule 1 ◽  
Store Operated Calcium Entry ◽  
Specific Proteins ◽  
Thyroid Cancer Cell Lines ◽  
And Function

AbstractStromal interaction molecule 1 (STIM1) and the ORAI1 calcium channel mediate store-operated calcium entry (SOCE) and regulate a multitude of cellular functions. The identity and function of these proteins in thyroid cancer remain elusive. We show that STIM1 and ORAI1 expression is elevated in thyroid cancer cell lines, compared to primary thyroid cells. Knock-down of STIM1 or ORAI1 attenuated SOCE, reduced invasion, and the expression of promigratory sphingosine 1-phosphate and vascular endothelial growth factor-2 receptors in thyroid cancer ML-1 cells. Cell proliferation was attenuated in these knock-down cells due to increased G1 phase of the cell cycle and enhanced expression of cyclin-dependent kinase inhibitory proteins p21 and p27. STIM1 protein was upregulated in thyroid cancer tissue, compared to normal tissue. Downregulation of STIM1 restored expression of thyroid stimulating hormone receptor, thyroid specific proteins and increased iodine uptake. STIM1 knockdown ML-1 cells were more susceptible to chemotherapeutic drugs, and significantly reduced tumor growth in Zebrafish. Furthermore, STIM1-siRNA-loaded mesoporous polydopamine nanoparticles attenuated invasion and proliferation of ML-1 cells. Taken together, our data suggest that STIM1 is a potential diagnostic and therapeutic target for treatment of thyroid cancer.

scholarly journals miR-145 suppresses thyroid cancer growth and metastasis and targets AKT3

2014 ◽  
Vol 21 (4) ◽  
pp. 517-531 ◽  
Author(s):  
Myriem Boufraqech ◽  
Lisa Zhang ◽  
Meenu Jain ◽  
Dhaval Patel ◽  
Ryan Ellis ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Needle Aspiration ◽  
Cancer Growth ◽  
Akt Pathway ◽  
Thyroid Cell ◽  
Differentiation Markers ◽  
Thyroid Cells ◽  
Thyroid Cancer Cell Lines ◽  
And Function

The expression and function of miR-145 in thyroid cancer is unknown. We evaluated the expression and function of miR-145 in thyroid cancer and its potential clinical application as a biomarker. We found that the expression of miR-145 is significantly downregulated in thyroid cancer as compared with normal. Overexpression of miR-145 in thyroid cancer cell lines resulted in: decreased cell proliferation, migration, invasion, VEGF secretion, and E-cadherin expression. miR-145 overexpression also inhibited the PI3K/Akt pathway and directly targetedAKT3.In vivo, miR-145 overexpression decreased tumor growth and metastasis in a xenograft mouse model, and VEGF secretion. miR-145 inhibition in normal primary follicular thyroid cells decreased the expression of thyroid cell differentiation markers. Analysis of indeterminate fine-needle aspiration samples showed miR-145 had a 92% negative predictive value for distinguishing benign from malignant thyroid nodules. Circulating miR-145 levels were significantly higher in patients with thyroid cancer and showed a venous gradient. Serum exosome extractions revealed that miR-145 is secreted. Our findings suggest that miR-145 is a master regulator of thyroid cancer growth, mediates its effect through the PI3K/Akt pathway, is secreted by the thyroid cancer cells, and may serve as an adjunct biomarker for thyroid cancer diagnosis.

scholarly journals Stimulation of Cultured H9 Human Embryonic Stem Cells with Thyroid Stimulating Hormone Does Not Lead to Formation of Thyroid-Like Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Mykola I. Onyshchenko ◽  
Igor G. Panyutin ◽  
Irina V. Panyutin ◽  
Ronald D. Neumann
Keyword(s):  
Stem Cells ◽  
Thyroid Cancer ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Thyroid Stimulating Hormone ◽  
Definitive Endoderm ◽  
Human Escs ◽  
Thyroid Cells ◽  
Stimulating Hormone

The sodium-iodine symporter (NIS) is expressed on the cell membrane of many thyroid cancer cells, and is responsible for the radioactive iodine accumulation. However, treatment of anaplastic thyroid cancer is ineffective due to the low expression of NIS on cell membranes of these tumor cells. Human embryonic stem cells (ESCs) provide a potential vehicle to study the mechanisms of NIS expression regulation during differentiation. Human ESCs were maintained on feeder-independent culture conditions. RT-qPCR and immunocytochemistry were used to study differentiation marker expression,125I uptake to study NIS function. We designed a two-step protocol for human ESC differentiation into thyroid-like cells, as was previously done for mouse embryonic stem cells. First, we obtained definitive endoderm from human ESCs. Second, we directed differentiation of definitive endoderm cells into thyroid-like cells using various factors, with thyroid stimulating hormone (TSH) as the main differentiating factor. Expression of pluripotency, endoderm and thyroid markers and125I uptake were monitored throughout the differentiation steps. These approaches did not result in efficient induction of thyroid-like cells. We conclude that differentiation of human ESCs into thyroid cells cannot be induced by TSH media supplementation alone and most likely involves complicated developmental patterns that are yet to be understood.

scholarly journals WOMEN IN CANCER THEMATIC REVIEW: Thyroid-stimulating hormone in thyroid cancer: does it matter?

2016 ◽  
Vol 23 (11) ◽  
pp. T109-T121 ◽  
Author(s):  
Hannah Nieto ◽  
Kristien Boelaert
Keyword(s):  
Thyroid Cancer ◽  
High Risk ◽  
Thyroid Nodules ◽  
Cancer Recurrence ◽  
Needle Aspiration ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Cells ◽  
Invasive Approach ◽  
Serum Tsh ◽  
Stimulating Hormone

Differentiated thyroid cancer is the most common endocrine malignancy and the incidence is increasing rapidly worldwide. Appropriate diagnosis and post-treatment monitoring of patients with thyroid tumours are critical. Fine needle aspiration cytology remains the gold standard for diagnosing thyroid cancer, and although there have been significant refinements to this technique, diagnostic surgery is often required for patients suspected to have malignancy. Serum thyroid-stimulating hormone (TSH) is higher in patients with malignant thyroid nodules than in those with benign disease, and TSH is proportionally increased in more aggressive tumours. Importantly, we have shown that the pre-operative serum TSH concentration independently predicts the presence of malignancy in subjects presenting with thyroid nodules. Establishing the use of TSH measurements in algorithms identifying high-risk thyroid nodules in routine clinical practice represents an exciting, cost-efficient and non-invasive approach to optimise thyroid cancer diagnosis. Binding of TSH to receptors on thyrocytes stimulates a number of growth promoting pathways both in normal and malignant thyroid cells, and TSH suppression with high doses of levothyroxine is routinely used after thyroidectomy to prevent cancer recurrence, especially in high-risk tumours. This review examines the relationship between serum TSH and thyroid cancer and reflects on the clinical potential of TSH measurements in diagnosis and disease monitoring.

scholarly journals Metformin Reverts the Secretion of CXCL8 Induced by TNF-α in Primary Cultures of Human Thyroid Cells: An Additional Indirect Anti-Tumor Effect of the Drug

2015 ◽  
Vol 100 (3) ◽  
pp. E427-E432 ◽  
Author(s):  
Mario Rotondi ◽  
Francesca Coperchini ◽  
Patrizia Pignatti ◽  
Flavia Magri ◽  
Luca Chiovato
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Primary Cultures ◽  
Human Thyroid ◽  
Thyroid Cells ◽  
Cxcl8 Secretion ◽  
Tnf Α ◽  
Thyroid Cancer Cell Lines ◽  
Thyroid Cancer Cells

Context: Metformin displays both direct and indirect anti-tumor effects. CXCL8 is a crucial downstream mediator of Nuclear-Factor-κB signaling related to the growth and progression of thyroid cancers. Targeting CXCL8 results in prolonged survival and reduced metastatic spread in in-vivo animal models of thyroid tumors. Objective: This study aimed to evaluate whether metformin inhibits the secretion of CXCL8 induced by Tumor-Necrosis-Factor-α (TNF-α) in primary cultures of normal and tumor human thyroid cells as well as in thyroid cancer cell lines. Methods: Normal human thyrocytes, papillary thyroid cancer cells, and thyroid cancer cell lines (TPC-1 and BCPAP) were stimulated with TNF-α (10 ng/mL) alone or in combination with metformin (0.01, 0.1, 1, 2.5, 5, and 10mM). CXCL8 levels were measured in the cell supernatants after 24 hours. Results: Metformin significantly and dose-dependently inhibited the TNF-α-induced CXCL8 secretion in both normal thyrocytes (ANOVA: F = 42.04; P < .0001) and papillary thyroid cancer cells (ANOVA: F = 21.691; P < .0001) but not in TPC-1 and BCPAP cell lines. Conclusion: Metformin inhibits the TNF-α-induced CXCL8 secretion in primary cultures of normal thyroid cells and differentiated thyroid cancer cells at least of the most frequent poorly aggressive phenotype. The recruitment of neutrophils within the thyroid gland is a crucial metastasis-promoting factor, and it depends on the amount of CXCL8 produced by both tumor cells and by the more abundant normal thyroid cells exposed to TNF-α. Thus, the here-reported inhibiting effect of metformin on TNF-α-induced CXCL8 secretion could be considered as a further indirect anticancer property of the drug.

scholarly journals Hypophysectomy abolishes rhythms in rat thyroid hormones but not in the thyroid clock

2017 ◽  
Vol 233 (3) ◽  
pp. 209-216 ◽  
Author(s):  
J Fahrenkrug ◽  
B Georg ◽  
J Hannibal ◽  
H L Jørgensen
Keyword(s):  
Thyroid Hormones ◽  
Clock Genes ◽  
Hormone Secretion ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Cells ◽  
Daily Rhythmicity ◽  
Nuclear Shuttling ◽  
The Individual ◽  
Rat Thyroid ◽  
And Function

The endocrine body rhythms including the hypothalamic–pituitary–thyroid axis seem to be regulated by the circadian timing system, and daily rhythmicity of circulating thyroid-stimulating hormone (TSH) is well established. The circadian rhythms are generated by endogenous clocks in the central brain oscillator located in the hypothalamic suprachiasmatic nucleus (SCN) as well as multiple peripheral clocks, but information on the existence and function of a thyroid clock is limited. The molecular machinery in all clock cells is composed of a number of clock genes and their gene products are connected by autoregulatory feedback loops. Here, we provide evidence for a thyroid clock in the rat by demonstrating 24-h antiphase oscillations for the mRNA of the canonical clock genes Per1 and Bmal1, which was unaffected by hypophysectomy. By immunostaining, we supported the existence of a core oscillator in the individual thyroid cells by demonstrating a daily cytoplasmatic–nuclear shuttling of PER1 protein. In normal rats, we found a significant daily rhythmicity in the circulating thyroid hormones preceded by a peak in TSH. In hypophysectomised rats, although the thyroid clock was not affected, the oscillations in circulating thyroid hormones were abolished and the levels were markedly lowered. No daily oscillations in the expression of TSH receptor mRNA were observed in neither control rats nor hypophysectomised rats. Our findings indicate that the daily rhythm of thyroid hormone secretion is governed by SCN signalling via the rhythmic TSH secretion rather than by the local thyroid clock, which was still ticking after hypophysectomy.

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