Figure 1.

Current concepts regarding stem cells and tumour evolution in tissues with ordered structure. (a) In normal tissue, adult stem cells (ASC) (yellow) self-renew and give rise to transit amplifying cells (TAC) (green) that divide several times before undergoing terminal differentiation (TD) (red). Many lines of evidence, including direct lineage tracing from genetically marked ASC, indicate that tumours arise from ASC, although an origin from TAC is also possible. (b) Tumours also have a hierarchical structure, albeit a relatively disorganized one. The cancer stem cells (CSCs) (yellow, blue border) may have a single phenotype and be rare or relatively common. (c) Genetic or epigenetic events may result in new clones driven by phenotypically diverse populations of CSCs. (d) Further genetic or epigenetic changes may result in some cells undergoing epithelial–mesenchymal transition (EMT), equipping them with CSC properties. (e) Metastasis may be caused by migrating CSCs detaching from the tumour mass; in particular, these may be the CSCs formed through EMT that may respond to chemotactic gradients by virtue of expression of chemokine receptors such as CXCR4.