Figure 1.

Model for the interplay between Myc and the microenvironment. When endogenous Myc is active (Myc on), insulinoma cells secrete VEGF and chemokines. These chemokines serve as chemoattractants for inflammatory cells, such as neutrophils and macrophages. These cells then secrete MMP9, leading to an increased availability of VEGF, up-regulated cell proliferation, and the survival of endothelial cells. In turn, these synergistic actions provide the tumor with sufficient oxygen and nutrients for expansion. Turning off Myc in the tumor cells (Myc off) leads to a first wave of apoptosis in the endothelial cell population and, subsequently, tumor regression due to hypoxia-induced apoptosis.