In-Silico Modeling of Tumor Spheroid Formation and Growth

Mathematical modeling has significant potential for understanding of biological models of cancer and to accelerate the progress in cross-disciplinary approaches of cancer treatment. In mathematical biology, solid tumor spheroids are often studied as preliminary in vitro models of avascular tumors. The size of spheroids and their cell number are easy to track, making them a simple in vitro model to investigate tumor behavior, quantitatively. The growth of solid tumors is comprised of three main stages: transient formation, monotonic growth and a plateau phase. The last two stages are extensively studied. However, the initial transient formation phase is typically missing from the literature. This stage is important in the early dynamics of growth, formation of clonal sub-populations, etc. In the current work, this transient formation is modeled by a reaction-diffusion partial differential equation (PDE) for cell concentration, coupled with an ordinary differential equation (ODE) for the spheroid radius. Analytical and numerical solutions of the coupled equations were obtained for the change in the radius of tumor spheroids over time. Human glioblastoma (hGB) cancer cells (U251 and U87) were spheroid cultured to validate the model prediction. Results of this study provide insight into the mechanism of development of solid tumors at their early stage of formation.