Figure 3.

The evolutionary (Panel A) and ecological dynamics (Panel B) of a successful metastasis by malignant tumor cells into a secondary site that offers similar conditions to the primary tumor. The secondary site offers an adaptive landscape similar to the primary site. At time 0 the normal cells of this organ are at a homeostatic equilibrium of u = 2 and x = 40; u = 2 maximizes carrying capacity for this organ but the normal cells are regulated to a much lower cell density. Even though the malignant tumor cells arrive with a strategy of v = 1.2 (optimal for the primary tumor shown in Fig. 1), the low density of normal cells means that the malignant cells still possess positive fitness and can grow in density. This gives the cancer cells time to evolve up the adaptive landscape. Initially they converge on the strategy of the normal cells of this novel organ but then continue evolving the more aggressive phenotype of u = 3.2 that is evolutionarily stable for the tumor cells of this secondary site. As the tumor cell’s density grows the normal cells initially can maintain their homeostatic equilibrium of x = 40. However, as time progresses (Panel A), the adaptive landscape becomes depressed as the tumor cells evolve (red line in Panel A) and their cell density increases (Panel B). For a successful metastasis, the recipient organ must offer a similar environment to the one for which the tumor cells have adapted. Yet, the metastasis will initially grow very slowly with little apparent change in the normal cell density because the normal cells initially inhibit and retard the evolutionary and ecological progression of the metastasis. But, once the tumor cells have converged on the strategy required for success in the novel organ, metastatic growth and evolution will accelerate