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Fig. 2 | BMC Cancer

Fig. 2

From: In vitro models of cancer stem cells and clinical applications

Fig. 2

Cancer stem cells reprogramming as an emerging tool in modelling cancer. The normal development (green arrows) denotes a passage from a pluripotent (zygote) to a “less potent state” (terminal differentiated adult tissues). During this process, adult stem cells (ASCs) in adult tissues suffer multiple tumorigenic “hits” that lead to the generation of “aberrantly reprogrammed” cancer cells, forced to be maintained in an intermediate degree of cellular differentiation (black arrow). Induced pluripotency is now being employed on cancer cell lines or patients’ tumours (named induced pluripotent cancer stem cells or iPCSCs) (blue arrows). iPCSCs cells epigenetically and transcriptionally resemble the ESC state and the cancer genome seems to be repressed in pluripotent state. In some cases the iPCSCs may exhibit early stage phenotypes corresponding to partial expression of the reprogrammed cancer genome, constituting in this way a live cell model to study cancer progression [69] (reviewed in [84]). Moreover, these iPCSCs have the ability to re-differentiate (orange arrow) back to the original or a different terminal differentiated cell lineage, losing along this process their tumorigenic and metastatic properties [110]. Alternatively, the induction to more differentiated state can occur directly from the adult tumour (in this case “trans-differentiation”-dashed blue arrow), without the need to pass first from the pluripotent state [61]. It is important to clarify the mechanisms controlling these transitions, as the ability to exogenously manipulate the stemness and differentiation of a tumour might hold promise as a therapeutic strategy in the near future

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