FIGURE 1.

In a primary niche, primary self-renewing cancer stem cells (CSC₁s) endowed with stemness properties, due to defined preimplantation checkpoint factors (OCT4, SOX2, NANOG, ID, CD44, HSP70, and HLA-G), would generate progressively secondary proliferating CSCs (CSC₂s), tertiary mesenchymal CSCs (CSC₃s), cancer progenitor (CPCs), and cancer differentiated (CDCs) cells, globally forming a tumor module where two zones would lie (quiescent and proliferating). In the proliferating zone, more external with normoxia conditions, CSC₃s and CPCs would proliferate, generating cell cord-finger structures on the invasive front at the tumor/host interface. On the other hand, in the quiescent zone, more internal with hypoxic conditions, quiescent CSC₃s would be induced to migrate peripherally, seeding new local niches in the normal host tissues. All these processes, finally, would result in a tumor module with a defined cell heterogeneity and hierarchy.