FIGURE 3.

Theoretical relationships between tumor gowth modules and avascular tumors. (A) Cord-finger structure of a tumor growth module. This image is directly extrapolated from the Figure 2B. (B) Theoretical modular growth in an avascular tumor: (a) Initial tumor growth module, located in the central zone, the future necrotic zone (black color). (b) and (c) Secondary tumor growth modules, arising from migrating CSC₃s, seeding via EMT/MET switch in surrounding niches, located in the sub-central zone, the future quiescent zone (blue color). Since nutrient diffusion limits are about 200 microns, the primary module comes to lie in the necrotic zone and dies, whereas the later modules located in the quiescent/proliferating zones (blue/green zones) grow, conferring a peripheral finger morphology on the structure. This structure could grow beyond defined limits only if its vascularization occurs, able to supply the necessary nutrients.