Stemness in Cancer: Stem Cells, Cancer Stem Cells, and Their Microenvironment

Figure 1

The origin of Cancer Stem Cells (CSCs) and Stem Cells (SCs) involvement in the generation of pathological cell hierarchies in tumors. In normal Stem Cell Systems, SCs located at the basal compartment generate committed progenitors (through asymmetrical divisions) which become spatially relocated to the transit-amplifying (TA) compartment. There, progenitors actively divide to produce differentiated daughter cells that carry on the normal physiology of the organ. Under physiological emergencies associated with SC loss, TA cells can dedifferentiate to reload the SC pool. Certain stressful triggers (i.e., chronic inflammation, ROS accumulation, and aging) can promote the transformation of cells in the system and generate CSCs or cancer initiating cells. CSCs remodel the niche and produce a pathological cancer microenvironment and associated hierarchy (pathological Stem Cell System) that resembles the original normal Stem Cell Systems (SCSs). The tumor is a very heterogeneous entity with cells that have accumulated mutations and epigenetic profile changes to secure CSCs survival and thriving. Features typical of SCSs such as niche support, SCs stemness, and dedifferentiation paths () remain in the tumor environment. SCs = Stem Cell; TA = transit-amplifying progenitor; TD = terminally differentiated cell; CSC = Cancer Stem Cell; CTA = cancer transit-amplifying progenitor; CTD = cancer terminally differentiated cell.