Three-dimensional (3D) culture has been increasingly used to investigate
tumor cell biology for improved simulation of the natural developing environment. However, the way in which 3D culture affects the gene expression and
biological functions of
glioma cells remains to be fully elucidated. In the present study, 3D culture environments were established using
collagen scaffolds with different pore sizes, followed by the comparison of gene expression profiles and associated
biological functions of
glioma cells, including the U87, U251 and HS683 cell lines, in 3D collagen scaffolds with conventional two-dimensional (2D) cultured cells. Finally, the possible signaling pathways regulating these differences were investigated. It was found that the 3D collagen scaffold culture upregulated the expression of genes associated with stemness, cell cycle, apoptosis, epithelia-mesenchymal transition, migration, invasion and
glioma malignancy, and induced the corresponding functional changes. Apoptotic pathways, the Wnt pathway, Sonic Hedgehog pathway and Notch pathway, may be involved in the regulation of these changes. The aperture size of the
collagen-scaffold did not appear to affect the gene expression or functions of the
glioma cells. The results of the study suggested that the 3D collagen scaffold enhanced the
malignancy of
glioma cells and may be a promising in vitro platform for investigations of
glioma.