Oscillating growth patterns of multicellular tumour spheroids

Abstract

The growth kinetics of 9L (rat glioblastoma cell line) and U118 (human glioblastoma cell line) multicellular tumour spheroids (MTS) have been investigated by non-linear least square fitting of individual growth curves with the Gompertz growth equation and power spectrum analysis of residuals. Residuals were not randomly distributed around calculated growth trajectories. At least one main frequency was found for all analysed MTS growth curves, demonstrating the existence of time-dependent periodic fluctuations of MTS volume dimensions. Similar periodic oscillations of MTS volume dimensions were also observed for MTS generated using cloned 9L cells. However, we found significant differences in the growth kinetics of MTS obtained with cloned cells if compared to the growth kinetics of MTS obtained with polyclonal cells. Our findings demonstrate that the growth patterns of three-dimensional tumour cell cultures are more complex than has been previously predicted using traditional continuous growth models.

Emerging Patterns in Tumor Systems: Simulating the Dynamics of Multicellular Clusters with an Agent-based Spatial Agglomeration Model

“…and adaptive biosystems (Chignola et al, 1990;Coffey, 1998;Deisboeck et al, 2001;DeHauwer et al, 1997;Kraus & Wolf, 1993;Posadas et al, 1996;Schwab & Pienta, 1996). In our computational model, self-organization is manifested in the behavior of virtual brain tumor cells, which are attracted to migrate towards a distant, nonreplenished nutrient source despite the obstacle of high mechanical confinement.…”

An Integrated Computational/Experimental Model of Tumor Invasion

“…This indicates that neither volume growth nor cell count of spheroids can be modeled by a simple exponential formulation and that spheroid volumes may fluctuate around the asymptotic volumes predicted by the Gompertz growth model (15). In fact, time-dependent oscillating patterns in tumor volumes superimposed on the Gompertz growth curve were observed for rat glioblastoma spheroids (16).…”

Damaging effects of gliadin on three-dimensional cell culture model

“…MCTSs were initiated according to Dolfini et al [6] , by seeding 2×10 5 cells/mL in 25 mL of complete medium in polycarbonate Erlenmeyer flasks (Corning, Milan, Italy), and incubated in a gyratory rotation incubator. MCTS volumes were evaluated according to Chignola et al [13] . On the 7 th d, MCTSs (mean±SD: 220±70 μm) were exposed to digested gliadin (PT-gliadin, 500 μg/mL) or BSA (PT-BSA, 500 μg/mL) in completely renewed medium for further 5 d, and subsequently taken for the evaluation of lactate dehydrogenase (LDH) release, GSH content and GSH-related enzyme activity, and morphological analysis.…”