Abstract
BACKGROUND: Glioblastoma (GB) is an aggressive brain cancer with an average survival of 14.6 months. Effective treatment is hindered by GB’s plasticity and invasive phenotype. Little is known regarding the molecular mechanisms driving invasion heterogeneity. MATERIAL AND METHODS: We developed a bioengineered model of brain-like matrix, which together with patient-derived spheroids, allows study of GB’s migration in vitro. Twenty patient-derived cell lines with different intrinsic (genomic, transcriptomic) characteristics in several extrinsic (extracellular matrix stiffness, hypoxia vs normoxia) conditions were tested. RESULTS: Time-lapse video analysis identified recurrent migratory phenotypes across the cell lines. GB’s subtype- proneural, neural, classical, and mesenchymal- did not cluster cell lines with similar migratory phenotypes. An increase in matrix stiffness led to a switch in migratory phenotype in certain cell lines. CONCLUSION: We have identified finite and periodic migration phenotypes of GB in different conditions.