Hyaluronic Acid Influences Amino Acid Metabolism via Differential L‐Type Amino Acid Transporter 1 Expression in the U87‐Malignant Glioma Cell Line

The Glioblastoma (GBM) tumor microenvironment is heterogeneous, complex, and is being increasingly understood as a significant contributor to tumor progression. In brain tumors, the extracellular matrix contains a large concentration of Hyaluronic acid (HA) that makes it important to study its role in cancer progression. In particular, abnormal accumulation of HA is observed in gliomas and is often associated with poor prognosis. In addition, HA is a polymer and its molecular weight (MW) distribution may influence tumor cell activity. Here, we evaluate the influence of the molecular weight of HA on tumor cell metabolism. We use a 2D cell culture approach to expose the U87-MG cell line to different HA MWs (10, 60, and 500 kDa) and glucose concentrations (0, 5.5, and 25 mM). Notably, we found that HA influences GBM amino acid metabolism via reduction in LAT1 transporter protein expression. We also report an influence on mitochondrial respiration levels and a difference in the accumulation of some key products of cell metabolic activity (lactic acid, glutamic acid and succinic acid). Overall, these results indicate that HA MW can influence GBM metabolic state, with implications for cell invasion and tumor progression.