Simulated microgravity alters differentiation and increases apoptosis in human follicular thyroid carcinoma cells.
This study focuses on the effects of simulated microgravity (0g) on the human follicular thyroid carcinoma cell line ML-1. Cultured on a three-dimensional clinostat, ML-1 cells formed three-dimensional MCTSs (MCTS diameter: 0.3 +/- 0.01 mm). After 24 and 48 h of clinorotation, the cells significantly decreased fT3 and fT4 secretion but up-regulated the thyroid-stimulating hormone-receptor expression as well as the production of vimentin, vinculin, and extracellular matrix proteins (collagen I and III, laminin, fibronectin, chondroitin sulfate) compared with controls. Furthermore, ML-1 cells grown on the clinostat showed elevated amounts of the apoptosis-associated Fas protein, of p53, and of bax but showed reduced quantities of bcl-2. In addition, signs of apoptosis became detectable, as assessed by terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick end labeling, 4', 6-diamidino-2-phenylindole staining, DNA laddering, and 85-kDa apoptosis-related cleavage fragments. These fragments resulted from enhanced 116-kDa poly(ADP-ribose)polymerase (PARP) activity and apoptosis. These observations suggest that clinorotation elevates intermediate filaments, cell adhesion molecules, and extracellular matrix proteins and simultaneously induces apoptosis in follicular thyroid cancer cells. In conclusion, our experiments could provide a regulatory basis for the finding that astronauts show low thyroid hormone levels after space flight, which may be explained by the increase of apoptosis in thyrocytes as a result of simulated 0g.
Grimm
Daniela
D
Institute of Clinical Pharmacology and Toxicology, Benjamin Franklin Medical Center, Freie Universität Berlin, Germany. dgrimm@zedat.fu-berlin.de
Bauer
Johann
J
Kossmehl
Peter
P
Shakibaei
Mehdi
M
Schöberger
Johann
J
Pickenhahn
Holger
H
Schulze-Tanzil
Gundula
G
Vetter
Roland
R
Eilles
Christoph
C
Paul
Martin
M
Cogoli
Augusto
A
D018263:Adenocarcinoma, Follicular / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D017209:Apoptosis; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D013963:Thyroid Hormones / Q000096:biosynthesis; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D014407:Tumor Cells, Cultured; D018474:Weightlessness Simulation
D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D013963:Thyroid Hormones