Background The impact of the absence of gravity on cancer cells is of great interest, especially today that space is more accessible than ever. Despite advances, few and contradictory data are available mainly due to different setup, experimental design and time point analyzed. Methods Exploiting a Random Positioning Machine, we dissected the effects of long-term exposure to simulated microgravity (SMG) on pancreatic cancer cells performing proteomic, lipidomic and transcriptomic analysis at 1, 7 and 9 days. Results Our results indicated that SMG affects cellular morphology through a time-dependent activation of Actin-based motility via Rho and Cdc42 pathways leading to actin rearrangement, formation of 3D spheroids and enhancement of epithelial-to-mesenchymal transition. Bioinformatic analysis reveals that SMG may activates ERK5/NF-κB/IL-8 axis that triggers the expansion of cancer stem cells with an increased migratory capability. These cells, to remediate energy stress and apoptosis activation, undergo a metabolic reprogramming orchestrated by HIF-1α and PI3K/Akt pathways that upregulate glycolysis and impair β-oxidation, suggesting a de novo synthesis of triglycerides for the membrane lipid bilayer formation. Conclusions SMG revolutionizes tumor cell behavior and metabolism leading to the acquisition of an aggressive and metastatic stem cell-like phenotype. These results dissect the time-dependent cellular alterations induced by SMG and pave the base for altered gravity conditions as new anti-cancer technology.

Neural stem/progenitor cells (NSPCs) are self-renewing and multipotent cells of the central nervous system where they give rise to neurons, astrocytes and oligodendrocytes both during embryogenesis and throughout adulthood, although only in a few discrete niches. NSPC can integrate and send a plethora of signals not only within the local microenvironment but also at distance, including the systemic macroenvironment. Extracellular vesicles (EVs) are currently envisioned as main players in cell-cell communication in basic and translational neuroscience where they are emerging as an acellular alternative in regenerative medicine. At present NSPC-derived EVs represent a largely unexplored area compared to EVs from other neural sources and EVs from other stem cells, i.e., mesenchymal stem cells. On the other hand, available data suggest that NSPC-derived EVs can play key roles on neurodevelopmental and adult neurogenesis, and they are endowed with neuroprotective and immunomodulatory properties, and even endocrine functions. In this review we specifically highlight major neurogenic and “non-neurogenic” properties of NSPC-EVs, the current knowledge on their peculiar cargos and their potential translational value.

This study focused on effects induced by short-term simulated microgravity (SMG) condition on primary cell culture from pre-pubertal Wistar rats testis. Cells were analyzed for cytoskeletal and Sex Hormone Binding Globulin (SHBG/ABP) changes by immunofluorescence technique, for antioxidant system exploiting RT-PCR and cell viability. Cells were cultured for 6 and 24h on a three-dimensional clinostat, Random Positioning Machine (RPM). At the end of each experiment, once stopped the RPM rotation, cells were either fixed in paraformaldehyde or lysed and RNA extracted. In cells exposed to SMG the cytoskeleton became disorganized, microtubules fragmented and SHBG was already undetectable after 6h of treatment. Moreover, various antioxidant systems significantly increased after 24h of SMG exposure. Initially, SMG seemed to disturb antioxidant protection strategies allowing the testes to support sperm production, thus generating an aging-like state of oxidative stress. Studies on changes induced by short-term altered gravity conditions, carried out in real microgravity, could give more information on steroidogenesis and germ cell differentiation within the testis exposed to this condition and confirm the validity of simulation approach.

In the time of space explorations, the effect of hyper-gravity on the human physiology is a topic relatively neglected. Nevertheless, astronauts have several experiences of hyper-gravity during their mission. The main disturbance of altered gravity can be imputed to cell cytoskeleton alteration and physiologic homeostasis of the body. Testis has been revealed to be an organ particularly sensible, to be affected by environmental alteration and physiological disturbance. This makes testis an organ eligible for investigating the alteration following exposure to altered gravity. In our study, mice were exposed to hypergravity (3g for 14 days) in Large Diameter Centrifuge. We have observed morphological alteration of the regular architecture of the seminiferous tubules of testis as well as an altered expression of factors involved in junctional complexes of Sertoli cells, responsible to assure the morpho-functional integrity of the organ. The expression of key receptors in the physiological performance, such as Androgen Receptors and Interstitial Cells Stimulating Hormone (ICSH) receptors have been found lower expressed. All these findings indicate the occurrence of altered physiological performance of the organ such as the reduction of the spermatozoa number and an altered relationships with the endocrine physiology following hypergravity exposure.