Figure 1

Flow chart of multi-scale agent-based cancer modeling. The model encompasses four biological scales: the molecular scale, the cellular scale, the micro-environmental scale and the tissue scale. The molecular scale consists of the EGFR signaling and cell cycle pathways (Figure 2). The cellular scale simulates the phenotypic switch of the tumor cells as determined by the molecular scale, the cell-cell and the cell-microenvironment interactions (Figure 3). The micro-environmental scale provides a connection between the micro-vasculature (angiogenesis) and the tumor cells. Tumor cells consume glucose and oxygen nutrients. The tumor growth factor alpha (TGFα) secreted by tumor cells triggers the EGFR signaling pathway, which in turn determines cell’s phenotype switch. Oxygen plays an important role in the cell cycle during the proliferation phase. The VEGF secreted by the tumor cells induces angiogenesis. The tissue scale focuses on angiogenesis (Figure 4). Blood vessel sprouts migrate and branch via tip endothelial cells' migration in response to VEGF chemotaxis and fibronectin haptotaxis.