Abstract
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.
Highlights
For cancer biologists, microgravity-based research is still an unusual terrain
TinhRe PloMngex-tpeerrmimexnptseornimEeanrtths. iAnfrteeralthμegSpimroBvoixd/Sehdenazdheoeup-8ermiinsssiiognhtinin2t0o11t,hiet gbercoawmtehcbleeahratvhiaotur of thyrosipdaccae-nfcloewr ncelfloslliincuwlaerigthhtylreosisdnecsasnecexrclucedllisngchaannygaedddtihtieoirnaplrsohliefearraftoiornc,escaelsl thadehyemsioignh, tgbreowinthduced in grobuehnadv-iboausre,danfadcitlhiteiesp.oTsth-filsighhetlpreesdulttos eivnadliucaatteedwthhaetthtehreμcgelwlsasshtihfteedtritgogwearrdforathleesse-ffagegctrsesosbivseerved in RPpMhenexotpyepreim[4e8n].tsAononthEearritnht.erAesfttienrgtfhinedSinimg Bwoaxs/Sthhaetntzhhe ocuon-8flumeniscseiosntatiuns 2o0f1a1,ceitllbceuclatumreeccolueladr that space-flown follicular thyroid cancer cells changed their proliferation, cell adhesion, growth behaviour, and the post-flight results indicated that the cells shifted toward a less-aggressive phenotype [48]
We recently investigated changes of SOX transcription factors on FTC-133 follicular thyroid cancer cells exposed to the rtahnredeomdapysosointioanrinangdmomachine positioning machine (RPM) and determined the mRNA expression of SOX9 and SOX11 in adherently growing and multicellular spheroids (MCS) cells [47]
Summary
Microgravity-based research is still an unusual terrain. Microgravity (μg) provides a physical condition that is not possible on Earth and interestingly, this condition may be ripe for studying cancer [1,2]. Hammond et al [3] reported an alteration of 1632 of the 10,000 analyzed genes relative to ground controls This was the first experiment to show that reduced gravity can affect a wide range of genes of in vitro cultured cells. Exposure of thyrocytes in a rotary cell culture system under the presence of keratinocyte growth factor (KGF) allowed the formation of artificial human thyroid organoids. They structurally resembled natural thyroid tissue [24]. Nthy-ori 3-1 thyrocytes were able to form 3D spheroids when exposed to an FRC or an RPM [25] This cell line was originally obtained from normal human primary thyrocytes transfected with a plasmid containing an origin-defective large T antigen SV40 genome [32]. Normal thyrocytes revealed changes in the cytoskeleton, shredding of their membranes, alterations in gene expression, protein synthesis and secretion and showed an increased amount of apoptosis and a change in growth behaviour
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