Figure 1

Characteristics of CSCs. CSCs are tumour-initiating cells that may result from malignant transformation of stem/progenitor cells, instigating the tumorigenic process. CSCs have been described to possess stem-like properties, such as self-renewal, proliferation and differentiation abilities, expression of pluripotent (e.g. Sox2, Oct4, Nanog) and functional (e.g. ALDH1, CD133⁺, CD34⁺CD38^-) markers, active signalling pathways (e.g. Notch, Hedgehog, Wnt), genetic and epigenetic profiles similar to stem cells, and capacity to form spheres in vitro. CSCs can be efficiently detected when injected in immunocompromised mice, as these cells, through their self-renewal and differentiation potential, give rise to a tumour with phenotypic heterogeneity. Tumorigenesis is followed by angiogenesis and by the invasion and metastatic stages, as part of the disease progression. Indeed, CSCs have been associated with the induction of tumour vascularisation through the expression of vascular-related factors and by their contribution to metastasis through the induction of the EMT program. Their resistance to chemo and radiotherapies is clinically important as most anticancer agents target the tumour bulk but not the CSC population. The resistance ability of these cells may be associated with their slow-cycling phenotype, and/or expression of efflux transporters, anti-apoptotic proteins, DNA-repair mechanisms, or of free radicals scavengers.