Microgravity-induced alterations in the molecular and cellular characteristics of brain tumors: a systematic review.

Background: Microgravity profoundly impacts various biological functions, including those crucial to tumorigenesis. Investigating the effects of microgravity on brain tumors is pivotal for understanding tumor biology and developing novel therapeutic strategies. This delineates the molecular and cellular characteristics of brain tumor cells under microgravity conditions. Methodology: The authors systematically reviewed the literature to identify relevant studies. Results: Microgravity has been shown to (i) induce morphological changes, where cultured glioma cells showed inhibited invasion through formation of multicellular aggregates, and ANGM5 glioblastoma multiforme (GBM) cell line showed 3D multicellular spheroid formation and loss of adhesion; (ii) inhibit cellular proliferation generally, as well as reduce invasion and migration in U87 GBM cells, however, cell viability remained high in A-172 GBM cells and human umbilical vein endothelial cells; (iii) increase DNA damage, evidenced by increased comet tail length and expression of phosphorylated γ-H2A.X, and activate apoptotic pathways in GBM and microglial cells; (iv) alter signaling pathways and protein expression through activation of ERK1/2 and AKT, altering the expression of GSK3β, Bax, and Bcl-2 in microglial and GBM cells, and through decreasing expression of vinculin and active Yap1 in GBM cells, and that of of Yap1 and ZO-1 in endothelial cells; and (v) increase chemosensitivity of GBM cells to cisplatin. Conclusion: Studies have shown that, across several rotary cell culture systems (RCCSs), random-position machines (RPMs), and 3D bioprinted GBM on-a-chip models, microgravity has consistently been proven to have profound effects on GBM cells. This further drills the potential role offered by microgravity as a promising anti-cancer agent in brain tumors, especially GBM.