{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T07:54:18Z","timestamp":1781250858354,"version":"3.54.1"},"reference-count":115,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T00:00:00Z","timestamp":1558656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsches Zentrum f\u00fcr Luft-und Raumfahrt","award":["50WB1524"],"award-info":[{"award-number":["50WB1524"]}]},{"DOI":"10.13039\/501100002946","name":"Deutsches Zentrum f\u00fcr Luft- und Raumfahrt","doi-asserted-by":"publisher","award":["50WB1124"],"award-info":[{"award-number":["50WB1124"]}],"id":[{"id":"10.13039\/501100002946","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002946","name":"Deutsches Zentrum f\u00fcr Luft- und Raumfahrt","doi-asserted-by":"publisher","award":["50WB1924"],"award-info":[{"award-number":["50WB1924"]}],"id":[{"id":"10.13039\/501100002946","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Microgravity in space or simulated by special ground-based devices provides an unusual but unique environment to study and influence tumour cell processes. By investigating thyroid cancer cells in microgravity for nearly 20 years, researchers got insights into tumour biology that had not been possible under normal laboratory conditions: adherently growing cancer cells detach from their surface and form three-dimensional structures. The cells included in these multicellular spheroids (MCS) were not only altered but behave also differently to those grown in flat sheets in normal gravity, more closely mimicking the conditions in the human body. Therefore, MCS became an invaluable model for studying metastasis and developing new cancer treatment strategies via drug targeting. Microgravity intervenes deeply in processes such as apoptosis and in structural changes involving the cytoskeleton and the extracellular matrix, which influence cell growth. Most interestingly, follicular thyroid cancer cells grown under microgravity conditions were shifted towards a less-malignant phenotype. Results from microgravity research can be used to rethink conventional cancer research and may help to pinpoint the cellular changes that cause cancer. This in turn could lead to novel therapies that will enhance the quality of life for patients or potentially develop new preventive countermeasures.<\/jats:p>","DOI":"10.3390\/ijms20102553","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T11:20:46Z","timestamp":1558696846000},"page":"2553","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Fighting Thyroid Cancer with Microgravity Research"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1120-0246","authenticated-orcid":false,"given":"Marcus","family":"Kr\u00fcger","sequence":"first","affiliation":[{"name":"Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Melnik","sequence":"additional","affiliation":[{"name":"Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Kopp","sequence":"additional","affiliation":[{"name":"Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Buken","sequence":"additional","affiliation":[{"name":"Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University, 39120 Magdeburg, Germany"},{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayashree","family":"Sahana","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann","family":"Bauer","sequence":"additional","affiliation":[{"name":"Max Planck Institute of Biochemistry, 82152 Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Wehland","sequence":"additional","affiliation":[{"name":"Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Hemmersbach","sequence":"additional","affiliation":[{"name":"Institute of Aerospace Medicine, Gravitational Biology, German Aerospace Center (DLR), Linder H\u00f6he, 51147 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3588-6350","authenticated-orcid":false,"given":"Thomas J.","family":"Corydon","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark"},{"name":"Department of Ophthalmology, Aarhus University Hospital, 8200 Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Infanger","sequence":"additional","affiliation":[{"name":"Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Grimm","sequence":"additional","affiliation":[{"name":"Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University, 39120 Magdeburg, Germany"},{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark"},{"name":"Gravitational Biology and Translational Regenerative Medicine, Faculty of Medicine and Mechanical Engineering, Otto von Guericke University, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/nrc3507","article-title":"Using space-based investigations to inform cancer research on earth","volume":"13","author":"Becker","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"394","DOI":"10.2174\/1568009614666140407113633","article-title":"Microgravity alters cancer growth and progression","volume":"14","author":"Jhala","year":"2014","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1152\/physiolgenomics.2000.3.3.163","article-title":"Mechanical culture conditions effect gene expression: Gravity-induced changes on the space shuttle","volume":"3","author":"Hammond","year":"2000","journal-title":"Physiol. Genom."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1152\/physiol.00036.2016","article-title":"Modeling physiological events in 2d vs. 3d cell culture","volume":"32","author":"Duval","year":"2017","journal-title":"Physiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/0360-3016(95)02065-9","article-title":"On the relation between size of necrosis and diameter of tumor spheroids","volume":"34","author":"Groebe","year":"1996","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"16691","DOI":"10.1038\/srep16691","article-title":"Mechanisms of three-dimensional growth of thyroid cells during long-term simulated microgravity","volume":"5","author":"Kopp","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/bcpt.12561","article-title":"Scaffold-free tissue formation under real and simulated microgravity conditions","volume":"119","author":"Aleshcheva","year":"2016","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"19103","DOI":"10.1038\/srep19103","article-title":"3d tumor spheroid models for in vitro therapeutic screening: A systematic approach to enhance the biological relevance of data obtained","volume":"6","author":"Zanoni","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_9","first-page":"3008","article-title":"Analysis of radiation effects in two irradiated tumor spheroid models","volume":"15","author":"Mortensen","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1002\/ijc.29251","article-title":"Thyroid cancer mortality and incidence: A global overview","volume":"136","author":"Malvezzi","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Albi, E., Kr\u00fcger, M., Hemmersbach, R., Lazzarini, A., Cataldi, S., Codini, M., Beccari, T., Ambesi-Impiombato, F.S., and Curcio, F. (2017). Impact of gravity on thyroid cells. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18050972"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Braddock, M. (2019). From target identification to drug development in space: Using the microgravity assist. Curr. Drug Discov. Technol.","DOI":"10.2174\/1570163816666190112150014"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s12217-013-9341-1","article-title":"Adaptation of a 2-d clinostat for simulated microgravity experiments with adherent cells","volume":"25","author":"Eiermann","year":"2013","journal-title":"Microgravity Sci. Technol."},{"key":"ref_15","first-page":"55","article-title":"Clinostats and bioreactors","volume":"14","author":"Klaus","year":"2001","journal-title":"Gravit. Space Biol. Bull."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s12217-008-9043-2","article-title":"Technology and developments for the random positioning machine, rpm","volume":"21","author":"Borst","year":"2008","journal-title":"Microgravity Sci. Technol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.asr.2007.02.016","article-title":"Some history and use of the random positioning machine, rpm, in gravity related research","volume":"39","year":"2007","journal-title":"Adv. Space Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/ast.2012.0876","article-title":"Ground-based facilities for simulation of microgravity: Organism-specific recommendations for their use and recommended terminology","volume":"13","author":"Herranz","year":"2013","journal-title":"Astrobiology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"971474","DOI":"10.1155\/2015\/971474","article-title":"Simulated microgravity: Critical review on the use of random positioning machines for mammalian cell culture","volume":"2015","author":"Wuest","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1155\/2014\/652863","article-title":"How microgravity changes galectin-3 in thyroid follicles","volume":"2014","author":"Albi","year":"2014","journal-title":"Biomed. Res. Int"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Masini, M.A., Albi, E., Barmo, C., Bonfiglio, T., Bruni, L., Canesi, L., Cataldi, S., Curcio, F., D\u2019Amora, M., and Ferri, I. (2012). The impact of long-term exposure to space environment on adult mammalian organisms: A study on mouse thyroid and testis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035418"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1089\/ast.2010.0519","article-title":"Thyrotropin receptor and membrane interactions in frtl-5 thyroid cell strain in microgravity","volume":"11","author":"Albi","year":"2011","journal-title":"Astrobiology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4172","DOI":"10.1210\/en.2002-0171","article-title":"Weightlessness induced apoptosis in normal thyroid cells and papillary thyroid carcinoma cells via extrinsic and intrinsic pathways","volume":"144","author":"Kossmehl","year":"2003","journal-title":"Endocrinology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1089\/thy.2000.10.481","article-title":"Thyroid organoid formation in simulated microgravity: Influence of keratinocyte growth factor","volume":"10","author":"Martin","year":"2000","journal-title":"Thyroid"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s12217-015-9456-7","article-title":"Thyroid cells exposed to simulated microgravity conditions \u2013 comparison of the fast rotating clinostat and the random positioning machine","volume":"28","author":"Warnke","year":"2016","journal-title":"Microgravity Sci. Technol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1159\/000480368","article-title":"Cytokine release and focal adhesion proteins in normal thyroid cells cultured on the random positioning machine","volume":"43","author":"Warnke","year":"2017","journal-title":"Cell Physiol. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9004","DOI":"10.1073\/pnas.91.19.9004","article-title":"Long-term culture and functional characterization of follicular cells from adult normal human thyroids","volume":"91","author":"Curcio","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1096\/fasebj.12.11.1007","article-title":"Spaceflight alters microtubules and increases apoptosis in human lymphocytes (jurkat)","volume":"12","author":"Lewis","year":"1998","journal-title":"FASEB J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"209","DOI":"10.4081\/1681","article-title":"Microgravity-induced apoptosis in cultured glial cells","volume":"46","author":"Uva","year":"2002","journal-title":"Eur. J. Histochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1096\/fj.11-199406","article-title":"5-lipoxygenase-dependent apoptosis of human lymphocytes in the international space station: Data from the roald experiment","volume":"26","author":"Battista","year":"2012","journal-title":"FASEB J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s10495-006-5697-7","article-title":"Induction of three-dimensional assembly and increase in apoptosis of human endothelial cells by simulated microgravity: Impact of vascular endothelial growth factor","volume":"11","author":"Infanger","year":"2006","journal-title":"Apoptosis"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/bjc.1989.387","article-title":"Characterisation of human thyroid epithelial cells immortalised in vitro by simian virus 40 DNA transfection","volume":"60","author":"Lemoine","year":"1989","journal-title":"Br. J. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.cyto.2014.07.006","article-title":"Low molecular weight hyaluronan mediated cd44 dependent induction of il-6 and chemokines in human dermal fibroblasts potentiates innate immune response","volume":"70","author":"Vistejnova","year":"2014","journal-title":"Cytokine"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11143","DOI":"10.1074\/jbc.RA118.003276","article-title":"Interleukin-6 promotes pancreatic cancer cell migration by rapidly activating the small gtpase cdc42","volume":"293","author":"Razidlo","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_35","first-page":"39","article-title":"Effects of simulated microgravity on thyroid carcinoma cells","volume":"501","author":"Grimm","year":"2002","journal-title":"Life Space Life Earth"},{"key":"ref_36","first-page":"295","article-title":"Simulated microgravity induces programmed cell death in human thyroid carcinoma cells","volume":"9","author":"Kossmehl","year":"2002","journal-title":"J. Gravit. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1038\/s41598-017-18556-8","article-title":"The role of nfkappab in spheroid formation of human breast cancer cells cultured on the random positioning machine","volume":"8","author":"Kopp","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_38","first-page":"P169","article-title":"Longterm conditions of mimicked weightlessness influences the cytoskeleton in thyroid cells","volume":"11","author":"Infanger","year":"2004","journal-title":"J. Gravit. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1159\/000331730","article-title":"Differential gene regulation under altered gravity conditions in follicular thyroid cancer cells: Relationship between the extracellular matrix and the cytoskeleton","volume":"28","author":"Ulbrich","year":"2011","journal-title":"Cell Physiol. Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s00441-005-0142-8","article-title":"Simulated weightlessness changes the cytoskeleton and extracellular matrix proteins in papillary thyroid carcinoma cells","volume":"324","author":"Infanger","year":"2006","journal-title":"Cell Tissue Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1096\/fj.13-236356","article-title":"The role of the cytoskeleton in sensing changes in gravity by nonspecialized cells","volume":"28","author":"Vorselen","year":"2014","journal-title":"FASEB J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s12217-015-9451-z","article-title":"Annotated gene and proteome data support recognition of interconnections between the results of different experiments in space research","volume":"28","author":"Bauer","year":"2016","journal-title":"Microgravity Sci. Technol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Riwaldt, S., Bauer, J., Wehland, M., Slumstrup, L., Kopp, S., Warnke, E., Dittrich, A., Magnusson, N.E., Pietsch, J., and Corydon, T.J. (2016). Pathways regulating spheroid formation of human follicular thyroid cancer cells under simulated microgravity conditions: A genetic approach. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17040528"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1002\/pmic.201000817","article-title":"A proteomic approach to analysing spheroid formation of two human thyroid cell lines cultured on a random positioning machine","volume":"11","author":"Pietsch","year":"2011","journal-title":"Proteomics"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Bauer, J., Kopp, S., Schlagberger, E.M., Grosse, J., Sahana, J., Riwaldt, S., Wehland, M., Luetzenberg, R., Infanger, M., and Grimm, D. (2017). Proteome analysis of human follicular thyroid cancer cells exposed to the random positioning machine. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030546"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1478-811X-12-32","article-title":"Spheroid formation of human thyroid cancer cells under simulated microgravity: A possible role of ctgf and cav1","volume":"12","author":"Warnke","year":"2014","journal-title":"Cell Commun. Signal."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Grimm, D., Bauer, J., Wise, P., Kr\u00fcger, M., Simonsen, U., Wehland, M., Infanger, M., and Corydon, T.J. (2019). The role of sox family members in solid tumours and metastasis. Semin. Cancer Biol.","DOI":"10.1016\/j.semcancer.2019.03.004"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1096\/fj.13-243287","article-title":"Differential gene expression profile and altered cytokine secretion of thyroid cancer cells in space","volume":"28","author":"Ma","year":"2014","journal-title":"FASEB J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"20043","DOI":"10.1038\/srep20043","article-title":"Alterations of the cytoskeleton in human cells in space proved by life-cell imaging","volume":"6","author":"Corydon","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"10355","DOI":"10.1038\/s41598-018-28695-1","article-title":"Thyroid cancer cells in space during the TEXUS-53 sounding rocket mission-the thyroid project","volume":"8","author":"Kopp","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Kopp, S., Kr\u00fcger, M., Bauer, J., Wehland, M., Corydon, T.J., Sahana, J., Nassef, M.Z., Melnik, D., Bauer, T.J., and Schulz, H. (2018). Microgravity affects thyroid cancer cells during the TEXUS-53 mission stronger than hypergravity. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19124001"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"28296","DOI":"10.3390\/ijms161226108","article-title":"The importance of caveolin-1 as key-regulator of three-dimensional growth in thyroid cancer cells cultured under real and simulated microgravity conditions","volume":"16","author":"Riwaldt","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.1002\/pmic.201500067","article-title":"Identification of proteins involved in inhibition of spheroid formation under microgravity","volume":"15","author":"Riwaldt","year":"2015","journal-title":"Proteomics"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Melnik, D., Kr\u00fcger, M., Kopp, S., Wehland, M., Bauer, J., Infanger, M., and Grimm, D. (2019). Microgravity-based modulation of VEGF expression in human thyroid carcinoma cells. Front. Physiol., 9.","DOI":"10.3389\/conf.fphys.2018.26.00002"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.3390\/ijms14011164","article-title":"Interaction of proteins identified in human thyroid cells","volume":"14","author":"Pietsch","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/s12217-011-9258-5","article-title":"Proteome analysis of thyroid cancer cells after long-term exposure to a random positioning machine","volume":"23","author":"Pietsch","year":"2011","journal-title":"Microgravity Sci. Technol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1002\/pmic.201200070","article-title":"Metabolic enzyme diversity in different human thyroid cell lines and their sensitivity to gravitational forces","volume":"12","author":"Pietsch","year":"2012","journal-title":"Proteomics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.jbi.2017.10.011","article-title":"Semantic analysis of thyroid cancer cell proteins obtained from rare research opportunities","volume":"76","author":"Bauer","year":"2017","journal-title":"J. Biomed. Inform."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Bauer, J., Wehland, M., Infanger, M., Grimm, D., and Gombocz, E. (2018). Semantic analysis of posttranslational modification of proteins accumulated in thyroid cancer cells exposed to simulated microgravity. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082257"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1080\/10826068.2018.1525567","article-title":"Preparative enrichment of human tissue cells capable to change a site of growth in vitro or in vivo-recent developments","volume":"48","author":"Bauer","year":"2018","journal-title":"Prep. Biochem. Biotechnol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5124","DOI":"10.1096\/fj.12-215749","article-title":"Gravity-sensitive signaling drives 3-dimensional formation of multicellular thyroid cancer spheroids","volume":"26","author":"Grosse","year":"2012","journal-title":"FASEB J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1006\/cbir.1999.0384","article-title":"Multicellular tumor spheroids: Intermediates between monolayer culture and in vivo tumor","volume":"23","year":"1999","journal-title":"Cell Biol. Int."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"7694","DOI":"10.1016\/j.biomaterials.2013.06.054","article-title":"Spheroid formation of human thyroid cancer cells in an automated culturing system during the shenzhou-8 space mission","volume":"34","author":"Pietsch","year":"2013","journal-title":"Biomaterials"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Svejgaard, B., Wehland, M., Ma, X., Kopp, S., Sahana, J., Warnke, E., Aleshcheva, G., Hemmersbach, R., Hauslage, J., and Grosse, J. (2015). Common effects on cancer cells exerted by a random positioning machine and a 2d clinostat. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135157"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e1800015","DOI":"10.1002\/pmic.201800015","article-title":"Decreased e-cadherin in mcf7 human breast cancer cells forming multicellular spheroids exposed to simulated microgravity","volume":"18","author":"Sahana","year":"2018","journal-title":"Proteomics"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1177\/1087057104265040","article-title":"The use of 3-d cultures for high-throughput screening: The multicellular spheroid model","volume":"9","author":"Freyer","year":"2004","journal-title":"J. Biomol. Screen"},{"key":"ref_67","first-page":"187","article-title":"Metastatic tumours in the thyreoid gland","volume":"7","author":"Willis","year":"1931","journal-title":"Am. J. Pathol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Schmidbauer, B., Menhart, K., Hellwig, D., and Grosse, J. (2017). Differentiated thyroid cancer-treatment: State of the art. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18061292"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1089\/thy.2014.0173","article-title":"Multi-organ distant metastases confer worse disease-specific survival in differentiated thyroid cancer","volume":"24","author":"Wang","year":"2014","journal-title":"Thyroid"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1308\/rcsann.2016.0300","article-title":"Patterns of metastasis in follicular thyroid carcinoma and the difference between early and delayed presentation","volume":"99","author":"Parameswaran","year":"2017","journal-title":"Ann. R. Coll. Surg. Engl."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1002\/dc.23773","article-title":"Cytological features of medullary thyroid carcinoma in ascitic effusion","volume":"45","author":"Rosa","year":"2017","journal-title":"Diagn Cytopathol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5127","DOI":"10.1038\/s41388-018-0317-x","article-title":"Multicellular detachment generates metastatic spheroids during intra-abdominal dissemination in epithelial ovarian cancer","volume":"37","author":"Kalos","year":"2018","journal-title":"Oncogene"},{"key":"ref_73","first-page":"101","article-title":"Multicellular spheroids. A review on cellular aggregates in cancer research","volume":"113","year":"1987","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0304-3835(98)00198-0","article-title":"Multicellular spheroids as an in vitro tumor model","volume":"131","author":"Hamilton","year":"1998","journal-title":"Cancer Lett."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3389\/fcell.2018.00017","article-title":"Feeling stress: The mechanics of cancer progression and aggression","volume":"6","author":"Northcott","year":"2018","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nrc2544","article-title":"A tense situation: Forcing tumour progression","volume":"9","author":"Butcher","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.tcb.2010.08.015","article-title":"Forcing form and function: Biomechanical regulation of tumor evolution","volume":"21","author":"Yu","year":"2011","journal-title":"Trends Cell Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"046603","DOI":"10.1088\/0034-4885\/77\/4\/046603","article-title":"Tensegrity, cellular biophysics and the mechanics of living systems","volume":"77","author":"Ingber","year":"2014","journal-title":"Rep. Prog. Phys."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1096\/fasebj.13.9001.s3","article-title":"How cells (might) sense microgravity","volume":"13","author":"Ingber","year":"1999","journal-title":"FASEB J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1159\/000486920","article-title":"Key proteins involved in spheroid formation and angiogenesis in endothelial cells after long-term exposure to simulated microgravity","volume":"45","author":"Dittrich","year":"2018","journal-title":"Cell Physiol. Biochem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3769","DOI":"10.1038\/s41598-018-20459-1","article-title":"Simulated microgravity inhibits cell focal adhesions leading to reduced melanoma cell proliferation and metastasis via fak\/rhoa-regulated mtorc1 and ampk pathways","volume":"8","author":"Tan","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Zhao, T., Li, R., Tan, X., Zhang, J., Fan, C., Zhao, Q., Deng, Y., Xu, A., Lukong, K.E., and Genth, H. (2018). Simulated microgravity reduces focal adhesions and alters cytoskeleton and nuclear positioning leading to enhanced apoptosis via suppressing fak\/rhoa-mediated mtorc1\/nf-kappab and ERK1\/2 pathways. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19071994"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1007\/s11626-019-00334-7","article-title":"Simulated microgravity inhibits the viability and migration of glioma via fak\/rhoa\/rock and fak\/nek2 signaling","volume":"55","author":"Deng","year":"2019","journal-title":"In Vitro Cell Dev. Biol. Anim."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1007\/s11626-013-9581-9","article-title":"Simulated microgravity alters the metastatic potential of a human lung adenocarcinoma cell line","volume":"49","author":"Chang","year":"2013","journal-title":"In Vitro Cell Dev. Biol. Anim."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.bbamcr.2006.07.001","article-title":"Regulation of the actin cytoskeleton in cancer cell migration and invasion","volume":"1773","author":"Yamaguchi","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1038\/onc.2013.166","article-title":"Profilin-1 downregulation has contrasting effects on early vs late steps of breast cancer metastasis","volume":"33","author":"Ding","year":"2014","journal-title":"Oncogene"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3892\/ijo.2014.2422","article-title":"Interleukin-6-induced epithelial-mesenchymal transition through signal transducer and activator of transcription 3 in human cervical carcinoma","volume":"45","author":"Miao","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.gene.2017.11.054","article-title":"Mmp9 gene expression regulation by intragenic epigenetic modifications in breast cancer","volume":"642","author":"Klassen","year":"2018","journal-title":"Gene"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s10555-007-9104-9","article-title":"Osteopontin: Regulation in tumor metastasis","volume":"27","author":"Wai","year":"2008","journal-title":"Cancer Metastasis Rev."},{"key":"ref_90","first-page":"1105","article-title":"Expression of interleukin-8 by human melanoma cells up-regulates mmp-2 activity and increases tumor growth and metastasis","volume":"151","author":"Luca","year":"1997","journal-title":"Am. J. Pathol."},{"key":"ref_91","first-page":"1213","article-title":"Tumor-derived vascular endothelial growth factor (vegf)-a facilitates tumor metastasis through the vegf-vegfr1 signaling pathway","volume":"39","author":"Liu","year":"2011","journal-title":"Int. J. Oncol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"320","DOI":"10.18632\/oncoscience.335","article-title":"Cd44: A metastasis driver and therapeutic target","volume":"3","author":"Sottnik","year":"2016","journal-title":"Oncoscience"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/j.1365-2265.2011.04183.x","article-title":"Decreased serum vascular endothelial growth factor-d levels in metastatic patients with differentiated thyroid carcinoma","volume":"76","author":"Nersita","year":"2012","journal-title":"Clin. Endocrinol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/jso.21844","article-title":"Vascular endothelial growth factors and angiopoietins in presentations and prognosis of papillary thyroid carcinoma","volume":"103","author":"Hsueh","year":"2011","journal-title":"J. Surg. Oncol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/s41526-017-0016-x","article-title":"Pyrocystis noctiluca represents an excellent bioassay for shear forces induced in ground-based microgravity simulators (clinostat and random positioning machine)","volume":"3","author":"Hauslage","year":"2017","journal-title":"NPJ Microgravity"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Wuest, S.L., Stern, P., Casartelli, E., and Egli, M. (2017). Fluid dynamics appearing during simulated microgravity using random positioning machines. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0170826"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1002\/pmic.200900226","article-title":"Application of free-flow ief to identify protein candidates changing under microgravity conditions","volume":"10","author":"Pietsch","year":"2010","journal-title":"Proteomics"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"10200","DOI":"10.1073\/pnas.0504754102","article-title":"Human isg15 conjugation targets both ifn-induced and constitutively expressed proteins functioning in diverse cellular pathways","volume":"102","author":"Zhao","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4995","DOI":"10.1016\/j.jmb.2013.09.041","article-title":"The antiviral activities of isg15","volume":"425","author":"Morales","year":"2013","journal-title":"J. Mol. Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jphs.2018.06.012","article-title":"Q63, a novel denv2 rdrp non-nucleoside inhibitor, inhibited denv2 replication and infection","volume":"138","author":"Yao","year":"2018","journal-title":"J. Pharmacol. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"R58","DOI":"10.1186\/bcr2117","article-title":"The ubiquitin-like molecule interferon-stimulated gene 15 (isg15) is a potential prognostic marker in human breast cancer","volume":"10","author":"Bektas","year":"2008","journal-title":"Breast Cancer Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1074\/jbc.271.2.695","article-title":"Discovery of a novel, potent and src family-selective tyrosine kinase inhibitor. Study of lck- and fynt-dependent t cell activation","volume":"271","author":"Hanke","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_103","first-page":"28","article-title":"Ameliorative effect of daidzein: A caveolin-1 inhibitor in vascular endothelium dysfunction induced by ovariectomy","volume":"50","author":"Sharma","year":"2012","journal-title":"Indian J. Exp. Biol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1089\/jir.2004.24.647","article-title":"Camptothecin induces the ubiquitin-like protein, isg15 and enhances isg15 conjugation in response to interferon","volume":"24","author":"Liu","year":"2004","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.12659\/MSM.898632","article-title":"High expression of rab-like 3 (rabl3) is associated with poor survival of patients with non-small cell lung cancer via repression of mapk8\/9\/10-mediated autophagy","volume":"22","author":"Zhang","year":"2016","journal-title":"Med. Sci. Monit."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1136\/gutjnl-2011-300304","article-title":"Pharmacological inhibition of the chemokine ccl2 (mcp-1) diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury","volume":"61","author":"Baeck","year":"2012","journal-title":"Gut"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"5429","DOI":"10.1128\/MCB.25.13.5429-5444.2005","article-title":"Blockade of histone deacetylase inhibitor-induced rela\/p65 acetylation and nf-kappab activation potentiates apoptosis in leukemia cells through a process mediated by oxidative damage, xiap downregulation and c-jun n-terminal kinase 1 activation","volume":"25","author":"Dai","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.4161\/15384101.2014.949550","article-title":"A small molecule fak kinase inhibitor, gsk2256098, inhibits growth and survival of pancreatic ductal adenocarcinoma cells","volume":"13","author":"Zhang","year":"2014","journal-title":"Cell Cycle"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.canlet.2017.12.022","article-title":"New microtubulin inhibitor mt189 suppresses angiogenesis via the jnk-vegf\/vegfr2 signaling axis","volume":"416","author":"Xu","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Wu, B., Li, J., Huang, D., Wang, W., Chen, Y., Liao, Y., Tang, X., Xie, H., and Tang, F. (2011). Baicalein mediates inhibition of migration and invasiveness of skin carcinoma through ezrin in a431 cells. BMC Cancer, 11.","DOI":"10.1186\/1471-2407-11-527"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jprot.2018.05.007","article-title":"Curcumin exerts its antitumor effects in a context dependent fashion","volume":"182","author":"Kreutz","year":"2018","journal-title":"J. Proteom."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3389\/fncel.2013.00161","article-title":"Radixin inhibition decreases adult neural progenitor cell migration and proliferation in vitro and in vivo","volume":"7","author":"Persson","year":"2013","journal-title":"Front. Cell Neurosci."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Placencio, V.R., Ichimura, A., Miyata, T., and DeClerck, Y.A. (2015). Small molecule inhibitors of plasminogen activator inhibitor-1 elicit anti-tumorigenic and anti-angiogenic activity. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0133786"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1016\/j.bbadis.2016.05.010","article-title":"Novel effects of sphingosylphosphorylcholine on invasion of breast cancer: Involvement of matrix metalloproteinase-3 secretion leading to wnt activation","volume":"1862","author":"Kim","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_115","first-page":"117","article-title":"Therapeutic targeting of neu1 sialidase with oseltamivir phosphate (tamiflu(r)) disables cancer cell survival in human pancreatic cancer with acquired chemoresistance","volume":"7","author":"Abdulkhalek","year":"2014","journal-title":"Onco Targets Ther."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/10\/2553\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:54:48Z","timestamp":1760187288000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/10\/2553"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,24]]},"references-count":115,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["ijms20102553"],"URL":"https:\/\/doi.org\/10.3390\/ijms20102553","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,24]]}}}