Figure 1.

Evolution of the cancer stem cell concept. The original concept (A) emerged on the basis of the stem cell theory in its original form [19] and on the reports about the exclusive ability of tumor cells expressing stem cell markers to induce tumor growth [38,43]. The modern concept (B) has been updated by introducing the concept of the cells-of-origin of tumors [58,61] and according to data obtained by genetic analysis combined with CSC-associated marker profiling [24] and lineage tracing analysis [59,60,62,63]. Notably, the relationship between the cells-of-origin of cancer and the CSCs is yet not well understood and the characteristics of both cell types may dynamically change. The process of the CSC differentiation involves the activation of the rare quiescent stem cell-like subpopulation which gives rise to the progenitor-like actively proliferating cells and the subsequent generation of non-stem cell-like, non-cycling, non-tumorigenic “differentiated” cancer cells.