title: Simulated weightlessness changes the cytoskeleton and extracellular matrix proteins in papillary thyroid carcinoma cells.
abstract: Studies of astronauts, experimental animals, and cells have shown that, after spaceflights, the function of the thyroid is altered by low-gravity conditions. The objective of this study was to investigate the cytoskeleton and extracellular matrix (ECM) protein synthesis of papillary thyroid cancer cells grown under zero g. We investigated alterations of ONCO-DG 1 cells exposed to simulated microgravity on a three-dimensional random-positioning machine (clinostat) for 30 min, 24 h, 48 h, 72 h, and 120 h (n=6, each group). ONCO-DG 1 cells grown under microgravity exhibited early alterations of the cytoskeleton and formed multicellular spheroids. The cytoskeleton was disintegrated, and nuclei showed morphological signs of apoptosis after 30 min. At this time, vimentin was increased. Vimentin and cytokeratin were highly disorganized, and microtubules (alpha-tubulin) did not display their typical radial array. After 48 h, the cytoskeletal changes were nearly reversed. The formation of multicellular spheroids continued. In parallel, the accumulation of ECM components, such as collagen types I and III, fibronectin, chondroitin sulfate, osteopontin, and CD44, increased. The levels of both transforming growth factor beta-1 (TGF-beta(1)) and TGF-beta receptor type II proteins were elevated from 24 h until 120 h clinorotation. Gene expression of TGF-beta(1) was clearly enhanced during culture under zero g. The amount of E-cadherin was enhanced time-dependently. We suggest that simulated weightlessness rapidly affects the cytoskeleton of papillary thyroid carcinoma cells and increases the amount of ECM proteins in a time-dependent manner.
authors.affiliation: Department of Trauma and Reconstructive Surgery, Charité University Medical School, Center of Space Medicine, Benjamin Franklin Medical Center, 12200, Berlin, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Infanger
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: Bauer
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kossmehl-Zorn
authors.forename: Augusto
authors.initials: A
authors.lastname: Cogoli
authors.forename: Francesco
authors.initials: F
authors.lastname: Curcio
authors.forename: Alexander
authors.initials: A
authors.lastname: Oksche
authors.forename: Markus
authors.initials: M
authors.lastname: Wehland
authors.forename: Reinhold
authors.initials: R
authors.lastname: Kreutz
authors.forename: Martin
authors.initials: M
authors.lastname: Paul
authors.forename: Daniela
authors.initials: D
authors.lastname: Grimm
mesh_terms: D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D018874:Spheroids, Cellular; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D018474:Weightlessness Simulation / Q000009:adverse effects*
chemical_list: D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D053773:Transforming Growth Factor beta1