  Experimental evidence suggests that epidermal growth factor receptor
(EGFR)-mediated activation of the signaling protein phospholipase C gamma plays
a critical role in a cancer cell's phenotypic decision to either proliferate or
to migrate at a given point in time. Here, we present a novel three-dimensional
multiscale agent-based model to simulate this cellular decision process in the
context of a virtual brain tumor. Each tumor cell is equipped with an EGFR
gene-protein interaction network module that also connects to a simplified cell
cycle description. The simulation results show that over time proliferative and
migratory cell populations not only oscillate but also directly impact the
spatio-temporal expansion patterns of the entire cancer system. The percentage
change in the concentration of the sub-cellular interaction network's molecular
components fluctuates, and, for the proliferation-to-migration switch we find
that the phenotype triggering molecular profile to some degree varies as the
tumor system grows and the microenvironment changes. We discuss potential
implications of these findings for experimental and clinical cancer research.
