Growth characteristics of glioblastoma spheroids

Cell spheroids have been proposed as models of early tumor growth from whic h a better understanding of tumor cell heterogeneity and its effects on tre atment response might be gained. Results of experiments performed to unders tand the underlying dynamics of cell growth within a spheroid formed by SNB 19, a high-grade glioblastoma cell line, are presented. We discuss the spa tiotemporal distribution of the cells and their cell cycle status based on physical measurements, immunohistochemistry, and flow cytometry analysis. T he size of the spheroids and their growth rates were dependent on the initi al cell number, the proliferation was mostly limited to the outermost regio n as the spheroids grew in size, and the number of dead cells increased wit h age and size as well. Interestingly, though the population of the prolife rating cells became localized to the outer rim as spheroids grew, the fract ion of proliferating cells did not change drastically. Also, our data revea l that the calculated density varied with respect to age of the spheroid as well as position within the spheroid. We show that a simple exponential mo del is not adequate for modelling the growth characteristics that have been seen by these experiments. In contradiction to available studies, we repor t that an acellular (necrotic) center appeared and then disappeared during the period of investigation. Furthermore, after the acellular region disapp eared, a few proliferative cells appeared in the center area, raising many questions about the growth-related dynamics of the spheroids formed by this particular cell type.