Number crunching in the cancer stem cell market

Abstract

Like their normal counterparts, many tumours are thought to have a hierarchical organization, albeit a disorganized one. Accordingly, the concept of cancer stem cells has emerged, and that these cells are responsible for perpetuating tumour existence. Operationally, cancer stem cells are regarded as prospectively purified cells that are the most effective at tumour initiation in an in vivo assay, usually after xenotransplantation to NOD/SCID mice. The conventional wisdom is that such tumour-initiating cells are rare based upon having to xenotransplant large numbers of human tumour cells into immunodeficient mice to propagate the tumour, but new evidence indicates that perhaps these cells are not so rare, at least in malignant melanoma, if a supportive soil is provided for the transplanted cells along with further restriction of the murine host's immune response.

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.