Background The epidermal growth factor receptor (EGFR) is frequently
overexpressed in many cancers, including non-small cell lung cancer (NSCLC). In
silcio modeling is considered to be an increasingly promising tool to add
useful insights into the dynamics of the EGFR signal transduction pathway.
However, most of the previous modeling work focused on the molecular or the
cellular level only, neglecting the crucial feedback between these scales as
well as the interaction with the heterogeneous biochemical microenvironment.
Results We developed a multiscale model for investigating expansion dynamics
of NSCLC within a two-dimensional in silico microenvironment. At the molecular
level, a specific EGFR-ERK intracellular signal transduction pathway was
implemented. Dynamical alterations of these molecules were used to trigger
phenotypic changes at the cellular level. Examining the relationship between
extrinsic ligand concentrations, intrinsic molecular profiles and microscopic
patterns, the results confirmed that increasing the amount of available growth
factor leads to a spatially more aggressive cancer system. Moreover, for the
cell closest to nutrient abundance, a phase-transition emerges where a minimal
increase in extrinsic ligand abolishes the proliferative phenotype altogether.
Conclusions Our in silico results indicate that, in NSCLC, in the presence of
a strong extrinsic chemotactic stimulus, and depending on the cell's location,
downstream EGFR-ERK signaling may be processed more efficiently, thereby
yielding a migration-dominant cell phenotype and overall, an accelerated
spatio-temporal expansion rate.Comment: 37 pages, 7 figure