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Simulated weightlessness changes the cytoskeleton and extracellular matrix proteins in papillary thyroid carcinoma cells

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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 (α–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-β1) and TGF-β receptor type II proteins were elevated from 24 h until 120 h clinorotation. Gene expression of TGF-β1 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.

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References

  • Adams JC, Watt FM (1993) Regulation of development and differentiation by the extracellular matrix. Development 117:1183–1198

    PubMed  CAS  Google Scholar 

  • Baghdassarian D, Torudel-Bauffe D, Gavaret JM, Pierre M (1993) Effects of transforming growth factor-beta-1 on the extracellular matrix and cytoskeleton of cultured astrocytes. Glia 7:193–202

    Article  PubMed  CAS  Google Scholar 

  • Brabant G, Hoang-Vu C, Cetin Y, Dralle H, Scheumann G, Molne J, Hansson G, Jansson S, Ericson LE, Nilsson M (1993) E-cadherin: a differentiation marker in thyroid malignancies. Cancer Res 53:4987–4993

    PubMed  CAS  Google Scholar 

  • Claisse D, Martiny I, Chaqour B, Wegrowski Y, Petitfrere E, Schneider C, Haye B, Bellon G (1999) Influence of transforming growth factor beta1 (TGF-beta1) on the behaviour of porcine thyroid epithelial cells in primary culture through thrombospondin-1 synthesis. J Cell Sci 112:1405–1416

    PubMed  CAS  Google Scholar 

  • Cogoli M (1992) The fast rotating clinostat: a history of its use in gravitational biology and a comparison of ground-based and flight experiment results. ASGSB Bull 5:59–67

    PubMed  CAS  Google Scholar 

  • Ernst H, Zanin MK, Everman D, Hoffman S (1995) Receptor-mediated adhesive and anti-adhesive functions of chondroitin sulfate proteoglycan preparations from embryonic chicken brain. J Cell Sci 108:3807–3816

    PubMed  CAS  Google Scholar 

  • Grimm D, Hofstädter F, Bauer J, Spruss T, Steinbach P, Bernhardt G, Menze R (1992) Establishment and characterization of a human papillary thyroid carcinoma cell line with oxyphilic differentiation (ONCO-DG 1). Virchows Arch 62:97–104

    CAS  Google Scholar 

  • Grimm D, Bauer J, Kromer E, Steinbach P, Riegger G, Hofstadter F (1995) Human follicular and papillary thyroid carcinoma cells interact differently with human venous endothelial cells. Thyroid 5:155–164

    PubMed  CAS  Google Scholar 

  • Grimm D, Bauer J, Hofstädter F, Riegger GAJ, Kromer EP (1997) Characteristics of multicellular spheroids formed by primary cultures of human thyroid tumor cells. Thyroid 7:859–865

    Article  PubMed  CAS  Google Scholar 

  • Grimm D, Huber M, Jabusch HC, Shakibaei M, Fredersdorf S, Paul M, Riegger GA, Kromer EP (2001) Extracellular matrix proteins in cardiac fibroblasts derived from rat hearts with chronic pressure overload: effects of β-receptor blockade. J Mol Cell Cardiol 33:487–501

    Article  PubMed  CAS  Google Scholar 

  • Grimm D, Bauer J, Kossmehl P, Shakibaei M, Schönberger J, Pickenhahn H, Schulze-Tanzil G, Vetter R, Eilles C, Paul M, Cogoli A (2002) Simulated microgravity alters differentiation and increases apoptosis in human follicular thyroid carcinoma cells. FASEB J 16:U55–U81

    Google Scholar 

  • Guarino V, Faviana P, Salvatore G, Castellone MD, Cirafici AM, De Falco V, Celetti A, Giannini R, Basolo F, Melillo RM, Santoro M (2005) Osteopontin is overexpressed in human papillary thyroid carcinomas and enhances thyroid carcinoma cell invasiveness. J Clin Endocrinol Metab 90:5270–5278

    Article  PubMed  CAS  Google Scholar 

  • Hagios C, Lochter A, Bissell MJ (1998) Tissue architecture: the ultimate regulator of epithelial function? Philos Trans R Soc Lond Biol 353:857–870

    Article  PubMed  CAS  Google Scholar 

  • Hoson T, Kamisaka S, Masuda Y, Yamashita M (1992) Changes in plant growth processes under microgravity conditions simulated by a three-dimensional clinostat. Bot Mag 105:53–70

    Article  Google Scholar 

  • Hughes-Fulford M, Lewis ML (1996) Effects of microgravity on osteoblast growth activation. Exp Cell Res 224:103–109

    Article  PubMed  CAS  Google Scholar 

  • Ingram M, Techy GB, Saroufeem R, Yazan O, Narayan KS, Goodwin TJ, Spaulding GF (1997) Three-dimensional growth patterns of various human tumor cell lines in simulated microgravity of a NASA bioreactor. In Vitro Cell Dev Biol Anim 33:459–466

    Article  PubMed  CAS  Google Scholar 

  • Kawata M, Sekiya S, Kera K, Kimura H, Takamizawa H (1991) Neural rosette formation within in vitro spheroids of a clonal human teratocarcinoma cell line, PA-1/NR: role of extracellular matrix components in the morphogenesis. Cancer Res 51:2655–2669

    PubMed  CAS  Google Scholar 

  • Khan SA, Lopez-Chua CA, Zhang J, Fisher LW, Sorensen ES, Denhardt DT (2002) Soluble osteopontin inhibits apoptosis of adherent endothelial cells deprived of growth factors. J Cell Biochem 85:728–736

    Article  PubMed  CAS  Google Scholar 

  • Khaoustov VI, Darlington GJ, Soriano HE, Krishnan B, Risin D, Pellis NR, Yoffe B (1999) Induction of three-dimensional assembly of human liver cells by simulated microgravity. In Vitro Cell Dev Biol Anim 35:501–550

    Article  PubMed  CAS  Google Scholar 

  • Kossmehl P, Shakibaei M, Cogoli A, Infanger M, Curcio F, Schoenberger J, Eilles C, Bauer J, Pickenhahn H, Schulze-Tanzil G, Paul M, Grimm D (2003) Weightlessness induced apoptosis in normal thyroid and carcinoma cells. Endocrinology 144:4172–4179

    Article  PubMed  CAS  Google Scholar 

  • Lelievre SA, Weaver VM, Nickerson JA, Larabell CA, Bhaumik A, Petersen OW, Bissell MJ (1998) Tissue phenotype depends on reciprocal interactions between the extracellular matrix and the structural organization of the nucleus. Proc Natl Acad Sci USA 95:14711–14716

    Article  PubMed  CAS  Google Scholar 

  • Lewis ML, Reynolds JL, Cubano LA, Hatton JP, Lawless BD, Piepmeier EH (1998) Spaceflight alters microtubules and increases apoptosis in human lymphocytes (Jurkat). FASEB J 12:1007–1018

    PubMed  CAS  Google Scholar 

  • Lewis ML, Cubano LA, Zhao BT, Dinh HK, Pabalan JG, Piepmeier EH, Bowman PD (2001) cDNA microarray reveals altered cytoskeletal gene expression in space-flown leukemic T lymphocytes (Jurkat). FASEB J 15:U277–U279

    Google Scholar 

  • Lin JD, Chao TC, Weng HF, Huang HS, Ho YS (1996) Establishment of xenografts and cell lines from well-differentiated human thyroid carcinoma. J Surg Oncol 63:112–118

    Article  PubMed  CAS  Google Scholar 

  • Maccarrone M, Battista N, Meloni M, Bari M, Galleri G, Pippia P, Cogoli A, Finazzi-Agro A (2003) Creating conditions similar to those that occur during exposure of cells to microgravity induces apoptosis in human lymphocytes by 5-lipoxygenase-mediated mitochondrial uncoupling and cytochrome c release. J Leukoc Biol 73:472–481

    Article  PubMed  CAS  Google Scholar 

  • Margolis L, Hatfill S, Chuaqui R, Vocke C, Emmert-Buck M, Linehan WM, Duray PH (1999) Long term organ culture of human prostate tissue in a NASA-designed rotating wall bioreactor. J Urol 161:290–297

    Article  PubMed  CAS  Google Scholar 

  • Martin A, Zhou A, Gordon RE, Henderson SC, Schwartz AE, Friedman EW, Davies TF (2000) Thyroid organoid formation in simulated microgravity: influence of keratinocyte growth factor. Thyroid 10:481–487

    PubMed  CAS  Google Scholar 

  • Merker HJ (1994) Morphology of the basement membrane. Microsc Res Tech 28:95–124

    Article  PubMed  CAS  Google Scholar 

  • Mukherjee BB, Nemir M, Beninati S, Cordella-Miele E, Singh K, Chackalaparampil I, Shanmugam V, DeVouge MW, Mukherjee AB (1995) Interaction of osteopontin with fibronectin and other extracellular matrix molecules. Ann N Y Acad Sci 760:201–212

    Article  PubMed  CAS  Google Scholar 

  • Nicogossian AE, Huntoon CL, Pool S (1989) In: Nicogossian AE (ed) Space physiology and medicine, 2nd edn. Lea and Febiger, Philadelphia

    Google Scholar 

  • O’Connor KC, Enmon RM, Dotson RS, Primavera AC, Clejan S (1997) Characterization of autocrine growth factors, their receptors and extracellular matrix present in three-dimensional cultures of DU 145 human prostate carcinoma cells grown in simulated microgravity. Tissue Eng 3:161–171

    Article  CAS  Google Scholar 

  • Roskelley CD, Desprez PY, Bissell MJ (1994) Extracellular matrix-dependent tissue-specific gene expression in mammary epithelial cells requires both physical and biochemical signal transduction. Proc Natl Acad Sci USA 91:12378–12382

    Article  PubMed  CAS  Google Scholar 

  • Schatten H, Lewis ML, Chakrabarti A (2001) Spaceflight and clinorotation cause cytoskeleton and mitochondria changes and increases in apoptosis in cultured cells. Acta Astronaut 49:399–418

    Article  PubMed  CAS  Google Scholar 

  • Schnee JM, Hsueh WA (2000) Angiotensin II, adhesion, and cardiac fibrosis. Cardiovasc Res 46:264–268

    Article  PubMed  CAS  Google Scholar 

  • Shakibaei M, Zimmermann B, Merker HJ (1995) Changes in integrin expression during chondrogenesis in vitro: an immunomorphological study. J Histochem Cytochem 43:1061–1069

    PubMed  CAS  Google Scholar 

  • Standal T, Borset M, Sundan A (2004) Role of osteopontin in adhesion, migration, cell survival and bone remodeling. Exp Oncol 26:179–184

    PubMed  CAS  Google Scholar 

  • Uva BM, Masini MA, Sturla M, Bruzzone F, Giuliani M, Tagliafierro G, Strollo F (2002) Microgravity-induced apoptosis in cultured glial cells. Eur J Histochem 46:209–214

    PubMed  CAS  Google Scholar 

  • Vassy J, Portet S, Beil M, Millot G, Fauvel-Lafeve F, Karniguian A, Gasset G, Irinopoulou T, Calvo F, Rigaut JP, Schoevaert D (2001) The effect of weightlessness on cytoskeleton architecture and proliferation of human breast cancer cell line MCF-7. FASEB J 15:1104–1106

    PubMed  CAS  Google Scholar 

  • White RJ, Averner M (2001) Humans in space. Nature 409:1115–1118

    Article  PubMed  CAS  Google Scholar 

  • Yurchenco PD, O’Rear JJ (1994) Basal lamina assembly. Curr Opin Cell Biol 6:674–681

    Article  PubMed  CAS  Google Scholar 

  • Zhou P, Qian L, Kozopas KM, Craig RW (1997) Mcl-1, a Bcl-2 family member, delays the death of hematopoietic cells under a variety of apoptosis-inducing conditions. Blood 89:630–643

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr. Chris Talsness for language editing. We are grateful to Roderick MacLeod for providing the CGTH-W-1 cell line.

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Correspondence to Daniela Grimm.

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The work of Augusto Cogoli was supported by ETH Zurich, Switzerland.

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Infanger, M., Kossmehl, P., Shakibaei, M. et al. Simulated weightlessness changes the cytoskeleton and extracellular matrix proteins in papillary thyroid carcinoma cells. Cell Tissue Res 324, 267–277 (2006). https://doi.org/10.1007/s00441-005-0142-8

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