ABSTRACT
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.
Subject(s)
Space Flight , Thyroid Neoplasms/metabolism , Weightlessness , Cell Line, Tumor , Extracellular Matrix/genetics , Extracellular Matrix/metabolism , Gene Expression Regulation, Neoplastic , Humans , Microarray Analysis , Polymerase Chain Reaction , Thyroid Neoplasms/geneticsABSTRACT
Human follicular thyroid cancer cells were cultured in Space to investigate the impact of microgravity on 3D growth. For this purpose, we designed and constructed a cell container that can endure enhanced physical forces, is connected to fluid storage chambers, performs media changes and cell harvesting automatically and supports cell viability. The container consists of a cell suspension chamber, two reserve tanks for medium and fixative and a pump for fluid exchange. The selected materials proved durable, non-cytotoxic, and did not inactivate RNAlater. This container was operated automatically during the unmanned Shenzhou-8 Space mission. FTC-133 human follicular thyroid cancer cells were cultured in Space for 10 days. Culture medium was exchanged after 5 days in Space and the cells were fixed after 10 days. The experiment revealed a scaffold-free formation of extraordinary large three-dimensional aggregates by thyroid cancer cells with altered expression of EGF and CTGF genes under real microgravity.
Subject(s)
Cell Culture Techniques/methods , Thyroid Neoplasms/pathology , Benzophenones , Bioreactors , Humans , Ketones , Polyethylene Glycols , Polymers , Real-Time Polymerase Chain Reaction , Space Flight , WeightlessnessABSTRACT
The altitude performance of two NO analysers using different NO detectors was studied. The analysers and their flow regulators were tested with simulated exhalations of reference gases. At 4000 m, volume flow was +35% and mass flow -24% of nominal in both instruments. The reduced mass flow increased the exhaled NO fraction by 26% for a given rate of NO excretion. Furthermore, the electrochemical NO detector in one analyser showed an increased signal level for a given partial pressure of test gas. Taken together, these two effects increased the signal output by 60% in comparison to the NO partial pressure. To avoid the above errors, it is proposed that the flow regulator should be readjusted to give a volume flow of 50 ml s(-1) at the altitude of interest and that the analyser should be recalibrated to the operational altitude. Finally, it is recommended that exhaled NO should always be reported as partial pressure and not as volume fraction, in order to compare measurements at any altitude.
