1Institute of Biomedicine, Pharmacology, Aarhus University, Wilhelm Meyers Allé 4, DK-8000 Aarhus C, Denmark.
FASEB J. 2014 Feb;28(2):813-35. doi: 10.1096/fj.13-243287. Epub 2013 Nov 6.
This study focuses on the effects of short-term [22 s, parabolic flight campaign (PFC)] and long-term (10 d, Shenzhou 8 space mission) real microgravity on changes in cytokine secretion and gene expression patterns in poorly differentiated thyroid cancer cells. FTC-133 cells were cultured in space and on a random positioning machine (RPM) for 10 d, to evaluate differences between real and simulated microgravity. Multianalyte profiling was used to evaluate 128 secreted cytokines. Microarray analysis revealed 63 significantly regulated transcripts after 22 s of microgravity during a PFC and 2881 after 10 d on the RPM or in space. Genes in several biological processes, including apoptosis (n=182), cytoskeleton (n=80), adhesion/extracellular matrix (n=98), proliferation (n=184), stress response (n=268), migration (n=63), angiogenesis (n=39), and signal transduction (n=429), were differentially expressed. Genes and proteins involved in the regulation of cancer cell proliferation and metastasis, such as IL6, IL8, IL15, OPN, VEGFA, VEGFD, FGF17, MMP2, MMP3, TIMP1, PRKAA, and PRKACA, were similarly regulated under RPM and spaceflight conditions. The resulting effect was mostly antiproliferative. Gene expression during the PFC was often regulated in the opposite direction. In summary, microgravity is an invaluable tool for exploring new targets in anticancer therapy and can be simulated in some aspects in ground-based facilities.
这项研究关注的是短期(22 秒,抛物线飞行实验)和长期(10 天,神舟八号太空任务)真实微重力对未分化甲状腺癌细胞细胞因子分泌和基因表达模式变化的影响。FTC-133 细胞在太空和转位器(RPM)上培养 10 天,以评估真实微重力和模拟微重力之间的差异。多分析物分析用于评估 128 种分泌细胞因子。微阵列分析显示,在抛物线飞行实验中,22 秒微重力后有 63 个基因显著调节,在 RPM 或太空中培养 10 天后有 2881 个基因显著调节。包括细胞凋亡(n=182)、细胞骨架(n=80)、黏附/细胞外基质(n=98)、增殖(n=184)、应激反应(n=268)、迁移(n=63)、血管生成(n=39)和信号转导(n=429)在内的多个生物学过程中的基因表达发生了变化。涉及调节癌细胞增殖和转移的基因和蛋白质,如 IL6、IL8、IL15、OPN、VEGFA、VEGFD、FGF17、MMP2、MMP3、TIMP1、PRKAA 和 PRKACA,在 RPM 和太空飞行条件下也受到类似的调节。其结果主要是抗增殖作用。抛物线飞行实验期间的基因表达通常以相反的方向调节。总之,微重力是探索抗癌治疗新靶点的宝贵工具,在某些方面可以在地面设施中模拟。