Abstract

Results: Exposing the cells to microgravity two phenotypes occurred: one part of the cells detached from the culture flask bottom and grew in form of 3D multicellular spheroids (MCS), the other one continued growing as a 2D monolayer. Interestingly, this 3D-formation occurred scaffold-free. MCS formed by thyroid cancer cells were more spherical aggregates, whereas endothelial cells exhibited both tube formation (intima constructs) and 3D MCS. Notably, the density of the monolayers exposed to microgravity had an impact on cell detachment and 3D structure formation. Genomic and proteomic alterations were induced by altered gravity conditions. Biological processes such as proliferation, migration, the composition of the extracellular matrix proteins, cell adhesion, focal adhesions, and apoptosis are influencing 3D growth under microgravity conditions. The gene expression patterns of growth factors (e.g. VEGF, EGF), extracellular matrix components (e.g. FN1), focal adhesion molecules (TLN1, VCL, CDH1) and cytokines (IL6, IL8) were differentially regulated and a large number of regulative factors have been shown to be involved in spheroid formation in microgravity.