  We studied the effects of epidermal growth factor receptor (EGFR) density on
tumor growth dynamics, both on the sub- and the multi-cellular level using our
previously developed model. This algorithm simulates the growth of a brain
tumor using a multi-scale two-dimensional agent-based approach with an
integrated transforming growth factor alpha (TGFalpha) induced
EGFR-gene-protein interaction network. The results confirm that increasing cell
receptor density correlates with an acceleration of the tumor system's
spatio-temporal expansion dynamics. This multicellular behavior cannot be
explained solely on the basis of spatial sub-cellular dynamics, which remain
qualitatively similar amongst the three glioma cell lines investigated here in
silico. Rather, we find that cells with higher EGFR density show an early
increase in the phenotypic switching activity between proliferative and
migratory traits, linked to a higher level of initial auto-stimulation by the
PLCgamma-mediated TGFalpha-EGFR autocrine network. This indicates a more active
protein level interaction in these chemotactically acting tumor systems and
supports the role of post-translational regulation for the implemented EGFR
pathway. Implications of these results for experimental cancer research are
discussed.
