Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany.
Department of Biomedicine, Aarhus University, Hoegh-Guldbergsgade 10, 8000 Aarhus C, Denmark.
Cells. 2020 Feb 5;9(2):367. doi: 10.3390/cells9020367.
Detachment and the formation of spheroids under microgravity conditions can be observed with various types of intrinsically adherent human cells. In particular, for cancer cells this process mimics metastasis and may provide insights into cancer biology and progression that can be used to identify new drug/target combinations for future therapies. By using the synthetic glucocorticoid dexamethasone (DEX), we were able to suppress spheroid formation in a culture of follicular thyroid cancer (FTC)-133 cells that were exposed to altered gravity conditions on a random positioning machine. DEX inhibited the growth of three-dimensional cell aggregates in a dose-dependent manner. In the first approach, we analyzed the expression of several factors that are known to be involved in key processes of cancer progression such as autocrine signaling, proliferation, epithelial-mesenchymal transition, and anoikis. Wnt/β-catenin signaling and expression patterns of important genes in cancer cell growth and survival, which were further suggested to play a role in three-dimensional aggregation, such as , , , (), or , were clearly affected by DEX. Our data suggest the presence of a more complex regulation network of tumor spheroid formation involving additional signal pathways or individual key players that are also influenced by DEX.
在微重力条件下,可以观察到各种类型的固有附着性人细胞的分离和球体的形成。特别是对于癌细胞,这个过程模拟了转移,可能为癌症生物学和进展提供一些见解,从而可以识别出用于未来治疗的新药/靶标组合。通过使用合成糖皮质激素地塞米松(DEX),我们能够抑制暴露于随机定位机上的改变重力条件的滤泡甲状腺癌细胞(FTC-133)培养物中的球体形成。DEX 以剂量依赖性方式抑制三维细胞聚集体的生长。在第一种方法中,我们分析了几种已知参与癌症进展关键过程的因子的表达,例如自分泌信号传导、增殖、上皮-间充质转化和失巢凋亡。Wnt/β-catenin 信号传导和在癌症细胞生长和存活中起重要作用的基因的表达模式,进一步表明在三维聚集中起作用,例如 、 、 ()或 、 ,明显受到 DEX 的影响。我们的数据表明,肿瘤球体形成涉及其他信号通路或受 DEX 影响的单个关键参与者的更复杂的调控网络的存在。