Discerning Glioblastoma Subpopulation Interactions through In Vitro Experiments and Mathematical Modeling

Glioblastoma is the most aggressive primary brain tumor with dismal median survival. Glioblastoma is known to be heterogeneous with multiple molecularly-distinct subpopulations, however, both the baseline change in growth with a given mutation and the compounded change due to dynamic interactions between subpopulations remain unknown. It is important to characterize these interactions for their potential impact on treatment resistance. Using both in vitro data and mathematical modeling, we aim to determine the interaction between two more-common glioblastoma subpopulations: amplification of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor alpha (PDGFRA). As a preliminary study, two glioblastoma cell lines, LN229 and GBM22, were identified with similar genetic profiles. Then, two variants of each of these lines were developed to over-express EGFR and PDGFRA, resulting in 6 molecularly-distinct cell lines in total. Variants of each cell line were allowed to grow both independently, and separately in co-culture with their sister variant. Preliminary calibration of an exponential model with the independently-grown cell culture data demonstrated that the variant influence on the growth rate was different between the cell lines. Future analysis will involve calibrating a system of reaction-diffusion equations to identify the effects of co-culturing these subpopulations on the growth kinetics.