Abstract
With the commercialization of spaceflight and the exploration of space, it is important to understand the changes occurring in human cells exposed to real microgravity (r-µg) conditions. We examined the influence of r-µg, simulated microgravity (s-µg, incubator random positioning machine (iRPM)), hypergravity (hyper-g), and vibration (VIB) on triple-negative breast cancer (TNBC) cells (MDA-MB-231 cell line) with the aim to study early changes in the gene expression of factors associated with cell adhesion, apoptosis, nuclear factor “kappa-light-chain-enhancer” of activated B-cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling. We had the opportunity to attend a parabolic flight (PF) mission and to study changes in RNA transcription in the MDA-MB cells exposed to PF maneuvers (29th Deutsches Zentrum für Luft- und Raumfahrt (DLR) PF campaign). PF maneuvers induced an early up-regulation of ICAM1, CD44 and ERK1 mRNAs after the first parabola (P1) and a delayed upregulation of NFKB1, NFKBIA, NFKBIB, and FAK1 after the last parabola (P31). ICAM-1, VCAM-1 and CD44 protein levels were elevated, whereas the NF-κB subunit p-65 and annexin-A2 protein levels were reduced after the 31st parabola (P31). The PRKCA, RAF1, BAX mRNA were not changed and cleaved caspase-3 was not detectable in MDA-MB-231 cells exposed to PF maneuvers. Hyper-g-exposure of the cells elevated the expression of CD44 and NFKBIA mRNAs, iRPM-exposure downregulated ANXA2 and BAX, whereas VIB did not affect the TNBC cells. The early changes in ICAM-1 and VCAM-1 and the rapid decrease in the NF-κB subunit p-65 might be considered as fast-reacting, gravity-regulated and cell-protective mechanisms of TNBC cells exposed to altered gravity conditions. This data suggest a key role for the detected gravity-signaling elements in three-dimensional growth and metastasis.
Highlights
The GLOBOCAN statistics from 2018 showed that breast cancer is the most common cancer in women and the second leading cause of cancer deaths worldwide [1]
The principal aim of this study was, first, to investigate the early phases of r-μg achieved by parabolic flight (PF) maneuvers on triple-negative breast cancer (TNBC) cells and to test whether there is a link between factors of apoptosis, changes in NF-κB signaling and cell adhesion
To examine whether the MDA-MB-231 cells were viable after the VIB, hyper-g, and incubator RPM (iRPM)-exposure, a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for the detection of DNA fragmentation was performed to measure the amount of apoptotic cells (Figure 1)
Summary
The GLOBOCAN statistics from 2018 showed that breast cancer is the most common cancer in women and the second leading cause of cancer deaths worldwide [1]. One important finding was that in r- and s-μg various cell types form three-dimensional (3D) aggregates called multicellular spheroids (MCS), resembling the in vivo situation of tumors much closer than conventional cell cultures [14]. These MCS are of great interest in cancer research to test drugs and to find new treatment targets [16]. Through drug-initiated NF-κB inhibition, they were able to reduce the formation of MCS As it is not clear when NF-κB signaling is triggered during MCS formation, we exposed MDA-MB-231 breast cancer cells to r-μg during a parabolic flight campaign (PFC)
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