Abstract
There are multiple definitions of cancer stem cells based on the different assays used to detect or enrich for them. The existence of different assays has made the identification and isolation of the archetypal cancer stem cell (CSC) with all of these properties an attractive but as yet unachievable goal. Indeed, it has been suggested that the lack of complementarity between these assays is in itself a barrier to CSC identification. Yet new insights into the heterogeneity of breast cancer stem cells and the discovery of CSC plasticity now suggests that rather than the existence of a single elusive stem-like entity in cancers, there may be a heterogeneous mix of cell populations able to switch their phenotype under different selective pressures. The aim of this review is to summarise the current evidence supporting this hypothesis and to suggest that focusing on the mechanisms controlling the inter-conversion between these minority stem cell populations could lead to more effective strategies to target the malignant properties of breast cancer stem cells.
Highlights
Models of tumourigenesis and the cancer stem cell hypothesisThe cancer stem cell (CSC) hypothesis first arose as a result of the noted similarities between normal stem cells and tumourigenic cells: both have the ability to self renew and to generate the heterogeneous cell populations observed in tissues and tumours
The gold standard of CSC identification, including breast cancer stem cells, continues to be tumour initiation with serial transplantation in recipient mice and most of the literature relies upon tumour initiation in vivo to identify and quantify stem-like cells from tumour cell populations
CD133 positive cells were shown to have stem-like properties comparable to the CD44+/CD24- populations isolated from other Brca null tumour cell lines, including similar gene expression profiles, significantly no overlap between the CD44+/24- and CD133+ population was Proposed Stem-like Characteristics Tumour initiation/ maintenance of tumour growth
Summary
The cancer stem cell (CSC) hypothesis first arose as a result of the noted similarities between normal stem cells and tumourigenic cells: both have the ability to self renew and to generate the heterogeneous cell populations observed in tissues and tumours. It has been proposed that some cancers may arise in a non-hierarchal manner, whereby transforming genetic lesions occur to multiple cells during the process of tumourigenesis This model of clonal evolution was initially put forward as an opponent of the cell-of-origin hypothesis; the two need not be mutually exclusive.
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