Interaction of matrix components and cells regulating cellular and molecular processes of glioma cells

The aberrant production of extracellular matrix (ECM) in gliomas results in aggressive tumor invasion. Hyaluronic acid (HA) and increased collagen production in the glioma matrix regulate tumor cell proliferation and migration. However, the regulatory effect of these molecules on glioma cells remains unclear. In this study, we analyzed the cell migration, proliferation, and transcriptome of glioma cells on collagen and HA substrates to understand the regulation of cellular processes. We found that both U87 and primary glioma cells showed a higher proliferation level on a collagen substrate compared with a hyaluronate substrate in an AlamarBlue® assay. U87 and primary glioma cells showed higher migration velocity on collagen substrate compared with hyaluronate substrate, a substrate of mixed collagen and hyaluronate, and collagen gels. The pathways enriched among genes up-regulated on collagen substrate versus hyaluronate substrate include focal adhesion, regulation of actin cytoskeleton, ECM-receptor interaction, and PI3K-Akt signaling pathways, which are involved in the regulation of cell migration. The up-regulated differentially expressed genes (DEGs) include integrin receptors, ECM molecules such as collagen types I, IV, and VI, fibronectin, and laminins, as well as signaling pathway molecules AKT3, RAC2, PIP5K1C, PIP4K2A, and PIK3R2. We also observed the upregulation of matrix metalloproteinase (MMP) genes and components of the glycosaminoglycan degradation pathway in glioma cells on the collagen matrix compared with those on HA matrix. This study reveals the effect of collagen and HA on glioma cells at the transcriptional level and contributes to the understanding of potential targets for therapy.