Cancer is a disease exhibiting uncontrollable cell growth and spreading to other parts of the organism. It is a heavy, worldwide burden for mankind with high morbidity and mortality. Therefore, groundbreaking research and innovations are necessary. Research in space under microgravity (µg) conditions is a novel approach with the potential to fight cancer and develop future cancer therapies. Space travel is accompanied by adverse effects on our health, and there is a need to counteract these health problems. On the cellular level, studies have shown that real (r-) and simulated (s-) µg impact survival, apoptosis, proliferation, migration, and adhesion as well as the cytoskeleton, the extracellular matrix, focal adhesion, and growth factors in cancer cells. Moreover, the µg-environment induces in vitro 3D tumor models (multicellular spheroids and organoids) with a high potential for preclinical drug targeting, cancer drug development, and studying the processes of cancer progression and metastasis on a molecular level. This review focuses on the effects of r- and s-µg on different types of cells deriving from thyroid, breast, lung, skin, and prostate cancer, as well as tumors of the gastrointestinal tract. In addition, we summarize the current knowledge of the impact of µg on cancerous stem cells. The information demonstrates that µg has become an important new technology for increasing current knowledge of cancer biology.

Microgravity changes the gene expression pattern in various cell types. This study focuses on the breast cancer cell lines MCF-7 (less invasive) and MDA-MB-231 (triple-negative, highly invasive). The cells were cultured for 14 days under simulated microgravity (s-µg) conditions using a random positioning machine (RPM). We investigated cytoskeletal and extracellular matrix (ECM) factors as well as focal adhesion (FA) and the transmembrane proteins involved in different cellular signaling pathways (MAPK, PAM and VEGF). The mRNA expressions of 24 genes of interest (TUBB, ACTB, COL1A1, COL4A5, LAMA3, ITGB1, CD44, VEGF, FLK1, EGFR, SRC, FAK1, RAF1, AKT1, ERK1, MAPK14, MAP2K1, MTOR, RICTOR, VCL, PXN, CDKN1, CTNNA1 and CTNNB1) were determined by quantitative real-time PCR (qPCR) and studied using STRING interaction analysis. Histochemical staining was carried out to investigate the morphology of the adherent cells (ADs) and the multicellular spheroids (MCSs) after RPM exposure. To better understand this experimental model in the context of breast cancer patients, a weighted gene co-expression network analysis (WGCNA) was conducted to obtain the expression profiles of 35 breast cell lines from the HMS LINCS Database. The qPCR-verified genes were searched in the mammalian phenotype database and the human genome-wide association studies (GWAS) Catalog. The results demonstrated the positive association between the real metastatic microtumor environment and MCSs with respect to the extracellular matrix, cytoskeleton, morphology, different cellular signaling pathway key proteins and several other components. In summary, the microgravity-engineered three-dimensional MCS model can be utilized to study breast cancer cell behavior and to assess the therapeutic efficacies of drugs against breast cancer in the future.

The primary objective of omics in space with focus on the human organism is to characterize and quantify biological factors that alter structure, morphology, function, and dynamics of human cells exposed to microgravity. This review discusses exciting data regarding genomics, transcriptomics, epigenomics, metabolomics, and proteomics of human cells and individuals in space, as well as cells cultured under simulated microgravity. The NASA Twins Study significantly heightened interest in applying omics technologies and bioinformatics in space and terrestrial environments. Here, we present the available publications in this field with a focus on specialized cells and stem cells exposed to real and simulated microgravity conditions. We summarize current knowledge of the following topics: (i) omics studies on stem cells, (ii) omics studies on benign specialized different cell types of the human organism, (iii) discussing the advantages of this knowledge for space commercialization and exploration, and (iv) summarizing the emerging opportunities for translational regenerative medicine for space travelers and human patients on Earth.

In this review article, we discuss the current state of knowledge in cancer research under real and simulated microgravity conditions and point out further research directions in this field. Outer space is an extremely hostile environment for human life, with radiation, microgravity, and vacuum posing significant hazards. Although the risk for cancer in astronauts is not clear, microgravity plays a thought-provoking role in the carcinogenesis of normal and cancer cells, causing such effects as multicellular spheroid formation, cytoskeleton rearrangement, alteration of gene expression and protein synthesis, and apoptosis. Furthermore, deleterious effects of radiation on cells seem to be accentuated under microgravity. Ground-based facilities have been used to study microgravity effects in addition to laborious experiments during parabolic flights or on space stations. Some potential ‘gravisensors’ have already been detected, and further identification of these mechanisms of mechanosensitivity could open up ways for therapeutic influence on cancer growth and apoptosis. These novel findings may help to find new effective cancer treatments and to provide health protection for humans on future long-term spaceflights and exploration of outer space.

We recently reported that synthetic glucocorticoid dexamethasone (DEX) is able to suppress metastasis-like spheroid formation in a culture of follicular thyroid cancer (FTC)-133 cells cultured under random positioning. We now show that this inhibition was selective for two metastatic thyroid carcinoma cells, FTC-133 and WRO, whereas benign Nthy-ori 3-1 thyrocytes and recurrent ML-1 follicular thyroid cancer cells were not affected by DEX. We then compare Nthy-ori 3-1 and FTC-133 cells concerning their adhesion and mechanosignaling. We demonstrate that DEX disrupts random positioning-triggered p38 stress signaling in FTC-133 cells, thereby antagonizing a variety of biological functions. Thus, DEX treatment of FTC-133 cells is associated with increased adhesiveness, which is mainly caused by the restored, pronounced formation of a normal number of tight junctions. Moreover, we show that Nthy-ori 3-1 and ML-1 cells upregulate the anti-adhesion protein mucin-1 during random positioning, presumably as a protection against mechanical stress. In summary, mechanical stress seems to be an important component in this metastasis model system that is processed differently by metastatic and healthy cells. The balance between adhesion, anti-adhesion and cell–cell connections enables detachment of adherent human cells on the random positioning machine—or not, allowing selective inhibition of thyroid in vitro metastasis by DEX.

In preparing space and microgravity experiments, the utilization of ground-based facilities is common for initial experiments and feasibility studies. One approach to simulating microgravity conditions on Earth is to employ a random positioning machine (RPM) as a rotary bioreactor. Combined with a suitable low-mass model system, such as cell cultures, these devices simulating microgravity have been shown to produce results similar to those obtained in a space experiment under real microgravity conditions. One of these effects observed under real and simulated microgravity is the formation of spheroids from 2D adherent cancer cell cultures. Since real microgravity cannot be generated in a laboratory on Earth, we aimed to determine which forces lead to the detachment of individual FTC-133 thyroid cancer cells and the formation of tumor spheroids during culture with exposure to random positioning modes. To this end, we subdivided the RPM motion into different static and dynamic orientations of cell culture flasks. We focused on the molecular activation of the mechanosignaling pathways previously associated with spheroid formation in microgravity. Our results suggest that RPM-induced spheroid formation is a two-step process. First, the cells need to be detached, induced by the cell culture flask’s rotation and the subsequent fluid flow, as well as the presence of air bubbles. Once the cells are detached and in suspension, random positioning prevents sedimentation, allowing 3D aggregates to form. In a comparative shear stress experiment using defined fluid flow paradigms, transcriptional responses were triggered comparable to exposure of FTC-133 cells to the RPM. In summary, the RPM serves as a simulator of microgravity by randomizing the impact of Earth’s gravity vector especially for suspension (i.e., detached) cells. Simultaneously, it simulates physiological shear forces on the adherent cell layer. The RPM thus offers a unique combination of environmental conditions for in vitro cancer research.