title: Simulated microgravity alters differentiation and increases apoptosis in human follicular thyroid carcinoma cells.
abstract: 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.
authors.affiliation: Institute of Clinical Pharmacology and Toxicology, Benjamin Franklin Medical Center, Freie Universität Berlin, Germany. dgrimm@zedat.fu-berlin.de
authors.forename: Daniela
authors.initials: D
authors.lastname: Grimm
authors.forename: Johann
authors.initials: J
authors.lastname: Bauer
authors.forename: Peter
authors.initials: P
authors.lastname: Kossmehl
authors.forename: Mehdi
authors.initials: M
authors.lastname: Shakibaei
authors.forename: Johann
authors.initials: J
authors.lastname: Schöberger
authors.forename: Holger
authors.initials: H
authors.lastname: Pickenhahn
authors.forename: Gundula
authors.initials: G
authors.lastname: Schulze-Tanzil
authors.forename: Roland
authors.initials: R
authors.lastname: Vetter
authors.forename: Christoph
authors.initials: C
authors.lastname: Eilles
authors.forename: Martin
authors.initials: M
authors.lastname: Paul
authors.forename: Augusto
authors.initials: A
authors.lastname: Cogoli
mesh_terms: 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
chemical_list: D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D013963:Thyroid Hormones