scholarly journals Activation of the mTOR/ Akt pathway in thymic epithelial cells derived from thymomas

2018 ◽  
Author(s):  
Jean-Michel Maury ◽  
Claire Merveilleux du Vignaux ◽  
Gabrielle Drevet ◽  
Virginie Zarza ◽  
Lara Chalabreysse ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cells ◽  
Cell System ◽  
Mtor Pathway ◽  
Thymic Epithelial Cells ◽  
Thymic Epithelial Tumors ◽  
Molecular Abnormalities ◽  
Short Period ◽  
Thymic Tumors

AbstractThe pathogenesis of thymic epithelial tumors remains poorly elucidated. The PI3K/Akt/mTOR pathway plays a key role in various cancers; interestingly, several phase I/II study reported a positive effect of mTOR inhibitors in disease control in thymoma patients. A major limit for deciphering cellular and molecular events leading to the transformation of thymic epithelial cells or for testing drug candidates is the lack of reliable in vitro cell systemWe analyzed protein expression and activation of key players of the Akt/mTOR pathway namely Akt, mTOR, and P70S6K in thirteen A, B and AB thymomas as well as in normal thymuses. While only Akt and the phospho-Akt were expressed in normal thymuses, both Akt and mTOR were activated, with B2 thymomas expressing higher level of activated phospho-Akt than A or AB subtypes. Phospho-P70S6K was expressed in all thymic tumors whatever their subtypes, and absent in normal thymus. Interestingly, in primary thymic epithelial cells maintained for short period of time after their derivation from seven AB and B thymomas, we report the activation of Akt; mTOR and P70S6. Finally, we analyzed the effect of mTOR inhibitor on thymoma derived epithelial cells and showed that rapamycin (100 nM/ ml) significantly reduced cell proliferation.Our results suggest that the activation of the Akt/ mTOR pathway might participate to the cell proliferation associated with tumor growth. Ultimately, our data enhance the potential role of thymic epithelial cells derived from tissue specimens forin vitroexploration of molecular abnormalities specific to rare thymic tumors.

Human thymic epithelial cells maintain long-term survival of clonogenic myeloid and erythroid progenitor cells in vitro

2000 ◽  
Vol 111 (1) ◽  
pp. 363-370 ◽  
Author(s):  
Katsuto Takenaka ◽  
Mine Harada ◽  
Tomoaki Fujisaki ◽  
Koji Nagafuji ◽  
Shinichi Mizuno ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Progenitor Cells ◽  
Thymic Epithelial Cells ◽  
Erythroid Progenitor ◽  
Term Survival ◽  
Long Term Survival ◽  
Erythroid Progenitor Cells

scholarly journals Modulation of IGF2 Expression in the Murine Thymus and Thymic Epithelial Cells Following Coxsackievirus-B4 Infection

2021 ◽  
Vol 9 (2) ◽  
pp. 402
Author(s):  
Hélène Michaux ◽  
Aymen Halouani ◽  
Charlotte Trussart ◽  
Chantal Renard ◽  
Hela Jaïdane ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Line ◽  
Thymic Epithelial Cells ◽  
Altered Expression ◽  
Coxsackievirus B4 ◽  
Gene Coding ◽  
Self Tolerance ◽  
Stat3 Phosphorylation ◽  
The Stability

Coxsackievirus B4 (CV-B4) can infect human and murine thymic epithelial cells (TECs). In a murine TEC cell line, CV-B4 can downregulate the transcription of the insulin-like growth factor 2 (Igf2) gene coding for the self-peptide of the insulin family. In this study, we show that CV-B4 infections of a murine TEC cell line decreased Igf2 P3 promoter activity by targeting a region near the transcription start site; however, the stability of Igf2 transcripts remained unchanged, indicating a regulation of Igf2 transcription. Furthermore, CV-B4 infections decreased STAT3 phosphorylation in vitro. We also showed that mice infected with CV-B4 had an altered expression of Igf2 isoforms as detected in TECs, followed by a decrease in the pro-IGF2 precursor in the thymus. Our study sheds new light on the intrathymic regulation of Igf2 transcription during CV-B4 infections and supports the hypothesis that a viral infection can disrupt central self-tolerance to insulin by decreasing Igf2 transcription in the thymic epithelium.

Effects of 2,3,7,8-TCDD and PCB 126 on human thymic epithelial cells in vitro

2003 ◽  
Vol 77 (6) ◽  
pp. 358-364 ◽  
Author(s):  
Kai Riecke ◽  
André Schmidt ◽  
Ralf Stahlmann
Keyword(s):  
Epithelial Cells ◽  
Thymic Epithelial Cells ◽  
Pcb 126

scholarly journals c-Src inactivation reduces renal epithelial cell-matrix adhesion, proliferation, and cyst formation

2011 ◽  
Vol 301 (2) ◽  
pp. C522-C529 ◽  
Author(s):  
Justine Elliott ◽  
Nadezhda N. Zheleznova ◽  
Patricia D. Wilson
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Collecting Duct ◽  
Specific Inhibitor ◽  
Cell Phenotype ◽  
Epithelial Cell Proliferation ◽  
Matrix Adhesion ◽  
Cyst Lining

c-Src is a non-receptor tyrosine kinase whose activity is induced by phosphorylation at Y418 and translocation from the cytoplasm to the cell membrane. Increased activity of c-Src has been associated with cell proliferation, matrix adhesion, motility, and apoptosis in tumors. Immunohistochemistry suggested that activated (pY418)-Src activity is increased in cyst-lining autosomal dominant polycystic kidney disease (ADPKD) epithelial cells in human and mouse ADPKD. Western blot analysis showed that SKI-606 (Wyeth) is a specific inhibitor of pY418-Src without demonstrable effects on epidermal growth factor receptor or ErbB2 activity in renal epithelia. In vitro studies on mouse inner medullary collecting duct (mIMCD) cells and human ADPKD cyst-lining epithelial cells showed that SKI-606 inhibited epithelial cell proliferation over a 24-h time frame. In addition, SKI-606 treatment caused a striking statistically significant decrease in adhesion of mIMCD and human ADPKD to extracellular collagen matrix. Retained viability of unattached cells was consistent with a primary effect on epithelial cell anchorage dependence mediated by the loss of extracellular matrix (ECM)-attachment due to α2β1-integrin function. SKI-606-mediated attenuation of the human ADPKD hyperproliferative and hyper-ECM-adhesive epithelial cell phenotype in vitro was paralleled by retardation of the renal cystic phenotype of Pkd1 orthologous ADPKD heterozygous mice in vivo. This suggests that SKI-606 has dual effects on cystic epithelial cell proliferation and ECM adhesion and may have therapeutic potential for ADPKD patients.

scholarly journals Human thymocytes bind to autologous and allogeneic thymic epithelial cells in vitro.

1986 ◽  
Vol 83 (17) ◽  
pp. 6588-6592 ◽  
Author(s):  
K. H. Singer ◽  
L. S. Wolf ◽  
D. F. Lobach ◽  
S. M. Denning ◽  
D. T. Tuck ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Thymic Epithelial Cells

scholarly journals Transgelin, a p53 and PTEN-Upregulated Gene, Inhibits the Cell Proliferation and Invasion of Human Bladder Carcinoma Cells in Vitro and in Vivo

2019 ◽  
Vol 20 (19) ◽  
pp. 4946 ◽  
Author(s):  
Tsui ◽  
Lin ◽  
Chang ◽  
Hou ◽  
Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cells ◽  
Bladder Carcinoma ◽  
Carcinoma Cells ◽  
Human Bladder ◽  
Ectopic Overexpression ◽  
Proliferation And Invasion ◽  
Bladder Carcinoma Cells

Transgelin (TAGLN/SM22-α) is a regulator of the actin cytoskeleton, affecting the survival, migration, and apoptosis of various cancer cells divergently; however, the roles of TAGLN in bladder carcinoma cells remain inconclusive. We compared expressions of TAGLN in human bladder carcinoma cells to the normal human bladder tissues to determine the potential biological functions and regulatory mechanisms of TAGLN in bladder carcinoma cells. Results of RT-qPCR and immunoblot assays indicated that TAGLN expressions were higher in bladder smooth muscle cells, fibroblast cells, and normal epithelial cells than in carcinoma cells (RT-4, HT1376, TSGH-8301, and T24) in vitro. Besides, the results of RT-qPCR revealed that TAGLN expressions were higher in normal tissues than the paired tumor tissues. In vitro, TAGLN knockdown enhanced cell proliferation and invasion, while overexpression of TAGLN had the inverse effects in bladder carcinoma cells. Meanwhile, ectopic overexpression of TAGLN attenuated tumorigenesis in vivo. Immunofluorescence and immunoblot assays showed that TAGLN was predominantly in the cytosol and colocalized with F-actin. Ectopic overexpression of either p53 or PTEN induced TAGLN expression, while p53 knockdown downregulated TAGLN expression in bladder carcinoma cells. Our results indicate that TAGLN is a p53 and PTEN-upregulated gene, expressing higher levels in normal bladder epithelial cells than carcinoma cells. Further, TAGLN inhibited cell proliferation and invasion in vitro and blocked tumorigenesis in vivo. Collectively, it can be concluded that TAGLN is an antitumor gene in the human bladder.

scholarly journals Pulmonary surfactant inhibition of nanoparticle uptake by alveolar epithelial cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
M. Radiom ◽  
M. Sarkis ◽  
O. Brookes ◽  
E. K. Oikonomou ◽  
A. Baeza-Squiban ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Pulmonary Surfactant ◽  
Fluid Layer ◽  
Alveolar Epithelial Cell ◽  
Cell System ◽  
Engineered Nanoparticles ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Inhaled Nanoparticles

Abstract Pulmonary surfactant forms a sub-micrometer thick fluid layer that covers the surface of alveolar lumen and inhaled nanoparticles therefore come in to contact with surfactant prior to any interaction with epithelial cells. We investigate the role of the surfactant as a protective physical barrier by modeling the interactions using silica-Curosurf-alveolar epithelial cell system in vitro. Electron microscopy displays that the vesicles are preserved in the presence of nanoparticles while nanoparticle-lipid interaction leads to formation of mixed aggregates. Fluorescence microscopy reveals that the surfactant decreases the uptake of nanoparticles by up to two orders of magnitude in two models of alveolar epithelial cells, A549 and NCI-H441, irrespective of immersed culture on glass or air–liquid interface culture on transwell. Confocal microscopy corroborates the results by showing nanoparticle-lipid colocalization interacting with the cells. Our work thus supports the idea that pulmonary surfactant plays a protective role against inhaled nanoparticles. The effect of surfactant should therefore be considered in predictive assessment of nanoparticle toxicity or drug nanocarrier uptake. Models based on the one presented in this work may be used for preclinical tests with engineered nanoparticles.

In vitro growth and maintenance of two morphologically distinct populations of thymic epithelial cells

1985 ◽  
Vol 90 (2) ◽  
pp. 439-450 ◽  
Author(s):  
A.C. Nieburgs ◽  
P.T. Picciano ◽  
J.H. Korn ◽  
T. McCalister ◽  
C. Allred ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Thymic Epithelial Cells ◽  
In Vitro Growth

Upregulated Expression of Fibronectin Receptors Underlines the Adhesive Capability of Thymocytes to Thymic Epithelial Cells During the Early Stages of Differentiation: Lessons From Sublethally Irradiated Mice

Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 974-990
Author(s):  
Sergio R. Dalmau ◽  
Claudia S. Freitas ◽  
Wilson Savino
Keyword(s):  
Epithelial Cells ◽  
Cell Attachment ◽  
Whole Body ◽  
Thymic Epithelial Cells ◽  
Strongly Correlated ◽  
Enhanced Expression ◽  
Single Positive ◽  
Young Stage ◽  
And Function

A 250-cGy whole-body γ-radiation dose was used to induce thymus regression in mice, and to study the expression and function of extracellular matrix (ECM) receptors in distinct thymocyte subsets emerging during repopulation of the organ. The onset of regeneration was detected from day 2 to 3 postirradiation (P-Ir), when a remarkable increase in the absolute counts of CD3−CD25hiCD44+ and CD3−CD25in/hiCD44−cells occurred. Enhanced expression of L-selectin, 4, and 5 integrin chains (L-selhi 4hi5hi) was also exhibited by these cells. This pattern of expression was maintained until the CD4+CD8+ (DP) young stage was achieved. Afterward, there was a general downregulation of these ECM receptors in DP as well as in CD4+ or CD8+ single positive (SP) thymocytes (L-selin 4in5in). In some recently generated SP cells, 4 expression was downregulated before the 5 chain, and L-selectin was upregulated in half of more mature cells. The expression of the 6 integrin chain was downregulated only in maturing CD4+cells. Importantly, the increased expression of L-selectin and 4 and 5 chains in thymocytes was strongly correlated with their adhesiveness to thymic epithelial cells (TEC) in vitro. Blocking experiments with monoclonal antibody or peptides showed the following: (1) that the LDV rather than the REDV cell attachment motif in the IIIC segment of fibronectin is targeted by the 4 integrin during thymocyte/TEC adhesion; (2) that the RGD motif of the 120-kD fragment of fibronectin, a target for 5 integrin, has a secondary role in this adhesion; and (3) that the YIGSR cell attachment motif of the β1 chain of laminin/merosin recognized by a nonintegrin receptor is not used for thymocyte adherence. In conclusion, our results show that an upregulated set of receptors endows CD25+ precursors and cells up to the young DP stage with a high capability of interacting with thymic ECM components.

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