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Spheroid formation of human thyroid cancer cells under simulated microgravity: a possible role of CTGF and CAV1

机译:模拟微重力作用下人甲状腺癌细胞的球状形成:CTGF和CAV1的可能作用

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Background Multicellular tumor spheroids (MCTS) formed scaffold-free under microgravity are of high interest for research and medicine. Their formation mechanism can be studied in space in real microgravity or on Earth using ground-based facilities (GBF), which simulate microgravity. On Earth, these experiments are more cost-efficient and easily performable. However, each GBF might exert device-specific and altered superimposingly gravity-dependent effects on the cells. Results FTC-133 human thyroid cancer cells were cultivated on a 2D clinostat (CN) and a random positioning machine (RPM) and compared with corresponding 1?g control cells. Harvested cell samples were investigated by microscopy, quantitative realtime-PCR and Multi-Analyte Profiling. Spheroid formation and growth occurred during 72?h of cultivation on both devices. Cytokine secretion and gene activation patterns frequently altered in different ways, when the cells were cultured either on the RPM or the CN. A decreased expression of CAV1 and CTGF in MCTS compared to adherent cells was observed after cultivation on both machines. Conclusion The development of MCTS proceeds similarly on the RPM and the CN resembling the situation observed under real microgravity conditions, while no MCTS formation was observed at 1?g under identical experimental conditions. Simultaneously, changes in the regulation of CTGF and CAV1 appeared in a comparable manner on both machines. A relationship between these molecules and MCTS formation is discussed.
机译:背景技术在微重力下无支架形成的多细胞肿瘤球体(MCTS)对于研究和医学具有很高的兴趣。可以使用模拟微重力的地面设施(GBF)在真实微重力的空间或地球上研究其形成机理。在地球上,这些实验更具成本效益且易于执行。但是,每个GBF都可能对细胞发挥特定于设备的作用,并且改变了重力依赖的叠加作用。结果FTC-133人甲状腺癌细胞在2D clinostat(CN)和随机定位仪(RPM)上培养,并与相应的1μg对照细胞进行比较。通过显微镜,定量实时PCR和多分析物分析研究收获的细胞样品。两种设备在培养72小时时均发生了球状体的形成和生长。当细胞在RPM或CN上培养时,细胞因子的分泌和基因激活模式经常以不同的方式改变。在两台机器上培养后,与贴壁细胞相比,观察到MCTS中CAV1和CTGF的表达降低。结论MCTS在RPM和CN上的发展相似,类似于在实际微重力条件下观察到的情况,而在相同的实验条件下,在1?g下未观察到MCTS的形成。同时,在两台机器上,CTGF和CAV1调节的变化以可比的方式出现。讨论了这些分子与MCTS形成之间的关系。

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