scholarly journals Fibronectin Is Required to Prevent Thyroid Cell Apoptosis through an Integrin-Mediated Adhesion Mechanism1

1998 ◽  
Vol 83 (10) ◽  
pp. 3673-3680 ◽  
Author(s):  
Mario Vitale ◽  
Tiziana Di Matola ◽  
Gianfranco Fenzi ◽  
Maddalena Illario ◽  
Guido Rossi
Keyword(s):  
Cell Line ◽  
Cell Apoptosis ◽  
Cultured Cells ◽  
Cell Types ◽  
Electrophoretic Analysis ◽  
Thyroid Cell ◽  
Control Mechanisms ◽  
Thyroid Cells ◽  
Flow Cytofluorometry ◽  
Cytoskeletal Organization

Apoptosis or programmed cell death occurs in a wide variety of cell types when adhesion to extracellular matrix (ECM) is denied. Invasion and metastasis by tumor cells involve the loss of normal cell-ECM contacts and require independence from such control mechanisms. We studied whether the immortalized thyroid cell line TAD-2 is a model suitable to investigate thyroid cell-ECM interaction, and we analyzed the role of integrin-fibronectin (FN) interaction in apoptosis. Adhesion, spreading, and cytoskeleton organization in TAD-2 cultured cells were dependent upon integrin-FN interaction. Cell spreading and cytoskeletal organization were coupled to deposition of insoluble FN induced by serum. Expression of integrin-FN receptors was demonstrated by flow cytofluorometry with specific antibodies, and strong integrin-dependent adhesion was demonstrated by attachment assays to immobilized FN. Apoptosis, occurring in different culture conditions, was determined by cell morphology and DNA electrophoretic analysis and quantitated by flow cytometry in propidium iodide-stained cells. Thyroid cells underwent apoptosis in the presence of serum when adhesion was prevented by specific peptides that inhibit integrin binding to FN (RGD-containing peptides) or by coating the culture plates with agar. In serum-free cultures, apoptosis was prevented by insoluble FN immobilized on the plates, but not by soluble FN. These results suggest that the TAD-2 cell line is a good model to study thyroid cell-ECM interaction, that FN, assembled into insoluble matrix, is required for cytoskeletal organization and to prevent thyroid cell apoptosis, and that integrin-mediated adhesion is involved in this process.

Adhesion molecule expression by the FRTL-5 rat thyroid cell line

1991 ◽  
Vol 130 (3) ◽  
pp. 451-456 ◽  
Author(s):  
N. Tandon ◽  
C. Dinsdale ◽  
T. Tamatani ◽  
M. Miyasaka ◽  
A. P. Weetman
Keyword(s):  
Cell Line ◽  
Adhesion Molecule ◽  
Interleukin 1 ◽  
Intercellular Adhesion Molecule ◽  
Thyroid Cell ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1 ◽  
Thyroid Cells ◽  
Thyroid Cell Line ◽  
Rat Thyroid

ABSTRACT We have examined the expression and function of rat CD54, a homologue of human intercellular adhesion molecule-1 (ICAM-1), by the continuously growing rat thyroid cell line FRTL-5. Approximately 10% of FRTL-5 cells express CD54 under basal conditions and this is not influenced by thyrotrophin. Expression of CD54 is increased by cytokines (γ-interferon, tumour necrosis factor, interleukin-1) and by an activator of C-kinase, phorbol 12-myristate 13-acetate. Blocking ICAM-1 with a monoclonal antibody directed against this molecule significantly (P <0·01) reduced the binding of splenic lymphocytes to FRTL-5 cells but inhibition was consistently greater (P <0·01) in the presence of antibodies against a rat homologue of lymphocyte function-associated antigen-1, the receptor on T cells for ICAM-1. In no case was complete blocking of cluster formation observed. These results show that a pure line of rat thyroid cells can express an ICAM-1 homologue and this is directly enhanced by cytokines. Expression of this homologue is partially responsible for lymphocyte adhesion to thyroid cells, which is likely to be a major event in T cell recognition of thyroid antigens in autoimmune thyroiditis. Journal of Endocrinology (1991) 130, 451–456

Role of non-TSH factors in thyroid cell growth

1987 ◽  
Vol 116 (1_Suppl) ◽  
pp. S231-S237 ◽  
Author(s):  
Margaret C. Eggo ◽  
Laura K. Bachrach ◽  
Gerard N. Burrow
Keyword(s):  
Dna Synthesis ◽  
Binding Proteins ◽  
Growth Stimulation ◽  
Cell Types ◽  
Thyroid Cell ◽  
Igf Binding Proteins ◽  
Thyroid Cells ◽  
Tetradecanoyl Phorbol Acetate ◽  
Biologic Effects ◽  
Igf Binding

Abstract. The effects of insulin, the tumour promotor tetradecanoyl phorbol acetate (TPA), TSH and combinations of these factors on growth and DNA synthesis have been examined in the FRTL-5 cell strain and in sheep thyroid cells. In addition the regulation of the production by sheep thyroid cells of the insulin-like growth factors (IGF) by TSH and their possible autocrine roles have been investigated. We found that insulin and the IGF's stimulated DNA synthesis in both rat FRTL-5 cells and sheep cells. TPA also stimulated growth in both cell types, and its effects were additive to those of insulin. In the FRTL-5 cells, TPA was a less potent stimulator of growth than TSH, but the effects of TPA and TSH were not additive which may imply growth stimulation through a common pathway. In sheep cells TSH was not mitogenic and did not appear to activate protein kinase C, the receptor for TPA. Sheep cells, unlike FRTL-5 cells, were found to produce IGF-I and IGF-II, and their syntheses were regulated by TSH. Sheep cells were also found to produce IGF-binding proteins which may modulate the biologic effects of the IGF's. Sheep thyroid IGF binding proteins were found to copurify with urokinase-like plasminogen activator on immunoaffinity chromatography. The production of this serine protease has also been shown to be regulated by TSH.

scholarly journals Pax-8 protein levels regulate thyroglobulin gene expression

1998 ◽  
Vol 21 (3) ◽  
pp. 347-354 ◽  
Author(s):  
D Fabbro ◽  
L Pellizzari ◽  
F Mercuri ◽  
G Tell ◽  
G Damante
Keyword(s):  
Promoter Activity ◽  
Expression Vector ◽  
Cell Types ◽  
Thyroid Cell ◽  
Critical Approach ◽  
Thyroid Cells ◽  
Protein Levels ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Thyroglobulin Gene

Pax proteins are transcription factors that control differentiation of several cell types. In adult organisms Pax-8 is expressed in the follicular thyroid cell where it interacts with sequences of thyroglobulin and thyroperoxidase promoters. In this study, we provide evidence indicating that Pax-8 protein levels regulate thyroglobulin gene transcription. The most critical approach consisted in increasing Pax-8 protein levels by transfecting thyroid cells with a Pax-8 expression vector. In this situation the thyroglobulin promoter transcriptional activity was significantly increased with respect to untransfected cells. In contrast, the transfection of thyroid transcription factor-1 (TTF-1) expression vector causes a modest decrease of thyroglobulin promoter activity, rather than an increase. Northern blots of human papillary cancers reveal a significant correlation between Pax-8 and thyroglobulin mRNAs. Gel-retardation assays suggest that the mechanism by which the Pax-8 protein levels modulate thyroglobulin promoter activity may occur through competition with TTF-1 for a common binding site. Since we also demonstrate that Pax-8 expression is subjected to TSH control, our data strongly suggest that Pax-8 protein levels could represent an important determinant for the regulation of thyroid cells.

Differential effects of interleukin 1α and 1β on cultured human and rat thyroid epithelial cells

1990 ◽  
Vol 122 (4) ◽  
pp. 520-526 ◽  
Author(s):  
Å. Krogh Rasmussen ◽  
L. Kayser ◽  
K. Bech ◽  
U. Feldt-Rasmussen ◽  
H. Perrild ◽  
...  
Keyword(s):  
Cell Line ◽  
Interleukin 1 ◽  
Cell System ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Camp Production ◽  
Thyroid Cells ◽  
Thyroid Cell Line ◽  
Interleukin 1Α ◽  
Rat Thyroid

Abstract The effects of human recombinant interleukin 1α (20 pg/1-2 μg/l) and 1β (200 pg/1-20 μg/l) on two systems of thyroid cells have been compared. The thyroglobulin and cAMP secretion and the DNA content of human thyroid cells cultured in monolayer and of continuously grown rat thyroid cells, Fischer rat thyroid cell line have been studied. The growth of the rat thyroid cell line was inhibited by interleukin 1β (20 ng/1-20 μg/l), but not by interleukin 1α. None of the cytokines changed the cAMP production of the rat thyroid cells. In contrast, both cAMP production and thyroglobulin secretion were inhibited dose-dependently by the cytokines in human thyroid cells in secondary cultures. These results caution the interpretation and extrapolation of changes induced by interleukin 1 from one cell system to the other.

scholarly journals Evidence that Human Thyroid Cells Express Uncleaved, Single-Chain Thyrotropin Receptors on Their Surface

Endocrinology ◽  
2006 ◽  
Vol 147 (6) ◽  
pp. 3107-3113 ◽  
Author(s):  
Chun-Rong Chen ◽  
Gregorio D. Chazenbalk ◽  
Kolja A. Wawrowsky ◽  
Sandra M. McLachlan ◽  
Basil Rapoport
Keyword(s):  
Cell Lines ◽  
Thyroid Tissue ◽  
Cell Types ◽  
Human Thyroid ◽  
Cross Linking ◽  
Thyroid Cell ◽  
Thyroid Cancer Cell ◽  
Single Chain ◽  
Thyroid Cells ◽  
Thyroid Cancer Cell Lines

Abstract The prevailing concept is that, in human thyroid tissue in vivo, all cell-surface TSH receptors (TSHR) cleave into disulfide linked A and B subunits. Because this viewpoint is based on studies using homogenized thyroid tissue and because of TSHR fragility, we studied TSHR subunit structure in intact thyroid cells, primary human thyrocyte cultures, FRTL-5 rat thyroid cells, and WRO (follicular) and NPA (papillary) thyroid cancer cell lines. To overcome the handicap of very low TSHR expression in thyroid cells, we generated a TSHR-expressing adenovirus (TSHR-Ad-RGD) with an integrin-binding RGD motif enabling efficient entry into cells lacking the coxsackie-adenovirus receptor. Two days after TSHR-Ad-RGD infection, [125I]TSH cross-linking to intact cells revealed uncleaved, single-chain TSHR as well as cleaved TSHR A subunits on the surface of all four thyroid cell types. The extent of TSHR cleavage, which is independent of the level of TSHR expression, was consistently lower in the human thyroid cancer cell lines than in the other cell lines. In flow cytometry studies after TSHR-Ad-RGD infection, strong signals were detected in all four thyroid cell types using a monoclonal antibody that primarily recognizes the uncleaved TSHR. Finally, using the same monoclonal antibody, confocal microscopy confirmed the presence of single-chain TSHR on TSHR-Ad-RGD-infected thyroid cells. In summary, TSH covalent cross-linking, flow cytometry, and confocal microscopy demonstrate the presence of uncleaved TSHR on the human thyrocyte surface. These data provide stronger evidence for this alternative than the contrary view based on the finding of only cleaved TSHR in homogenized thyroid cells.

scholarly journals Serum Withdrawal-Induced Apoptosis in Thyroid Cells Is Caused by Loss of Fibronectin-Integrin Interaction*

2000 ◽  
Vol 85 (3) ◽  
pp. 1188-1193 ◽  
Author(s):  
Tiziana Di Matola ◽  
Frank Mueller ◽  
Gianfranco Fenzi ◽  
Guido Rossi ◽  
Maurizio Bifulco ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Present Report ◽  
Annexin V ◽  
Cell Types ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Thyroid Cells ◽  
Serum Withdrawal ◽  
Induced Apoptosis ◽  
Rat Thyroid

Abstract In some cell types, including a fetal thyroid cell line, denial of adhesion to extracellular matrix induces a type of apoptosis called anoikis. Serum withdrawal in dog and transformed rat thyroid cells also induces programmed cell death. Because serum can stimulate cells to produce some components of the extracellular matrix, it was of interest to determine the role of the matrix in the apoptosis induced by serum withdrawal in normal human thyroid cells in primary culture. The present report demonstrates that thyroid cells selectively produce and deposit insoluble fibronectin (FN) only when stimulated by serum. Adhesion in the presence of serum is dependent upon integrin-FN interaction. Serum withdrawal determines a degradation of the insoluble FN deposited and a detachment of the cells from the plates. In these conditions, cells undergo anoikis, demonstrated by DNA fragmentation and annexin V staining. Apoptosis was prevented by exogenous FN immobilized onto the plates. These results indicate that serum withdrawal induces apoptosis in human thyroid cells, determining FN degradation and loss of cell-matrix adhesion.

scholarly journals Anion Selectivity by the Sodium Iodide Symporter

Endocrinology ◽  
2003 ◽  
Vol 144 (1) ◽  
pp. 247-252 ◽  
Author(s):  
J. Van Sande ◽  
C. Massart ◽  
R. Beauwens ◽  
A. Schoutens ◽  
S. Costagliola ◽  
...  
Keyword(s):  
Cell Line ◽  
Xenopus Oocytes ◽  
Sodium Iodide ◽  
Thyroid Cell ◽  
Sodium Iodide Symporter ◽  
Thyroid Cells ◽  
Anion Selectivity ◽  
Thyroid Cell Line ◽  
Competing Anions ◽  
Electrophysiological Methods

Abstract The iodide transporter of the thyroid (NIS) has been cloned by the group of Carrasco. The NIS-mediated transport was studied by electrophysiological methods in NIS-expressing Xenopus oocytes. Using this method, the anion selectivity of NIS was different from that previously reported for thyroid cells, whereas perchlorate and perrhenate were found not transported. In this study we compared the properties of human NIS, stably transfected in COS-7 cells to those of the transport in a thyroid cell line, the FRTL5 cells, by measuring the transport directly. We measured the uptake of 125I−, 186ReO4−, and 99mTcO4− and studied the effect on it of known competing anions, i.e. ClO4−, SCN−, ClO3−, ReO4−, and Br−. We conclude that the properties of the NIS transporter account by themselves for the properties of the thyroid iodide transporter as described previously in thyroid slices. The order of affinity was: ClO4− &gt; ReO4− &gt; I− ≥ SCN− &gt; ClO3− &gt; Br−. NIS is also inhibited by dysidenin (as in dog thyroid).

scholarly journals Association between the expression of E1A oncogene and increased sensitivity to growth inhibition induced by sustained levels of cAMP in rat thyroid cells

2000 ◽  
pp. 286-293 ◽  
Author(s):  
G Villone ◽  
G De Vita ◽  
P Chieffi ◽  
A Picascia ◽  
R Stanzione ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Latency Period ◽  
Polyoma Virus ◽  
Thyroid Cell ◽  
Intracellular Camp ◽  
Thyroid Cells ◽  
Rat Thyroid ◽  
Camp Levels ◽  
In Cells

OBJECTIVE: The aim of this study was to investigate: (i) whether a persistent increase of cAMP interferes with the proliferation of transformed thyroid cells, and (ii) whether the degree of malignancy is correlated with the sensitivity to a transient and/or sustained increase in intracellular cAMP levels. DESIGN AND METHODS: To address these questions we used thyroid cell lines transformed with E1A oncogene from adenoviruses 5 (PC E1A cell line) or 2 (PC HE4 cell line), or infected with the polyoma murine leukemia virus (PC PyMLV cell line) carrying the middle T gene of the polyoma virus, or, finally, expressing both E1A and PyMLV. These cell lines present various degrees of malignancy: PC EIA and PC HE4 cells are not tumorigenic; PC PyMLV cells induce non-invasive tumors after a long latency period; and PC EIA+PyMLV cells are highly tumorigenic. RESULTS AND CONCLUSIONS: Thyroid cell proliferation required the transient increase of intracellular cAMP levels, while persistent elevation of cAMP blocked the proliferation of normal thyroid PC Cl 3 cells and of PC Cl 3 cells transformed by a variety of different oncogenes. In addition, sustained levels of cAMP induced apoptosis in cells carrying the adenovirus EIA oncogene, but not in cells transformed with other oncogenes or in the wild-type PC Cl 3 cells. Furthermore, middle T gene of the polyoma virus seemed to afford protection only from apoptosis induced by cAMP when middle T is present in thyroid cells along with the E1A gene.

Regulation of thyroid cell volumes and fluid transport: opposite effects of TSH and iodide on cultured cells

2000 ◽  
Vol 279 (3) ◽  
pp. E546-E553 ◽  
Author(s):  
D. Cauvi ◽  
C. Penel ◽  
M. C. Nlend ◽  
N. Venot ◽  
C. Allasia ◽  
...  
Keyword(s):  
Cell Volume ◽  
Fluid Transport ◽  
Cultured Cells ◽  
Cell Volume Regulation ◽  
Thyroid Cell ◽  
Thyroid Cells ◽  
Mean Cell Volume ◽  
Control Value ◽  
The Mean ◽  
Cell Volumes

Cell volume regulation by thyrotropin (TSH) and iodide, the main effectors involved in thyroid function, was studied in cultured thyroid cells. The mean cell volume, determined by performing 3-D reconstitution on confocal microscopy optical slices from living octadecylrhodamine-labeled cells cultured with both TSH and iodide (control cells), was 3.73 ± 0.06 pl. The absence of iodide resulted in cell hypertrophy (136% of control value) and the absence of TSH in cell shrinkage (81%). These changes mainly affected the cell heights. The effect of TSH on cell volume was mediated by cAMP. The proportion of cytosolic volume (3- O-methyl-d-glucose space vs. total volume) decreased in the absence of iodide (85% of control value) and increased in the absence of TSH (139%), whereas protein content showed the opposite changes (121 and 58%, respectively). The net apical-to-basal fluid transport was also inversely controlled by the two effectors. Iodide thus antagonizes TSH effects on cell volumes and fluid transport, probably via adenylylcyclase downregulation mechanisms. The absence of either iodide or TSH may mimic the imbalance occurring in pathological thyroids.

scholarly journals Small Molecules and Peptides Targeting Glial Cell Line-Derived Neurotrophic Factor Receptors for the Treatment of Neurodegeneration

2020 ◽  
Vol 21 (18) ◽  
pp. 6575
Author(s):  
Yulia A. Sidorova ◽  
Mart Saarma
Keyword(s):  
Small Molecules ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Cultured Cells ◽  
Cell Types ◽  
The Body ◽  
Neuronal Populations ◽  
Pharmacokinetic Properties ◽  
Different Cell Types

Glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) are able to promote the survival of multiple neuronal populations in the body and, therefore, hold considerable promise for disease-modifying treatments of diseases and conditions caused by neurodegeneration. Available data reveal the potential of GFLs for the therapy of Parkinson’s disease, neuropathic pain and diseases caused by retinal degeneration but, also, amyotrophic lateral sclerosis and, possibly, Alzheimer’s disease. Despite promising data collected in preclinical models, clinical translation of GFLs is yet to be conducted. The main reasons for the limited success of GFLs clinical development are the poor pharmacological characteristics of GFL proteins, such as the inability of GFLs to cross tissue barriers, poor diffusion in tissues, biphasic dose-response and activation of several receptors in the organism in different cell types, along with ethical limitations on patients’ selection in clinical trials. The development of small molecules selectively targeting particular GFL receptors with improved pharmacokinetic properties can overcome many of the difficulties and limitations associated with the clinical use of GFL proteins. The current review lists several strategies to target the GFL receptor complex with drug-like molecules, discusses their advantages, provides an overview of available chemical scaffolds and peptides able to activate GFL receptors and describes the effects of these molecules in cultured cells and animal models.

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