Abstract
Cancer has long been viewed as an exclusively genetic disorder. The model of carcinogenesis, postulated by Nowell and Vogelstein, describes the formation of a tumor by the sequential accumulation of mutations in oncogenes and tumor suppressor genes. In this model, tumors are thought to consist of a heterogeneous population of cells that continue to acquire new mutations, resulting in a highly dynamic process, with clones that out compete others due to increased proliferative or survival capacity. However, novel insights in cancer stem cell research suggest another layer of complexity in the process of malignant transformation and preservation. It has been reported that only a small fraction of the cancer cells in a malignancy have the capacity to propagate the tumor upon transplantation into immuno-compromised mice. Those cells are termed ‘cancer stem cells’ (CSC) and can be selected based on the expression of cell surface markers associated with immature cell types. In this review, we will critically discuss these novel insights in CSC-related research. Where possible we integrate these results within the genetic model of cancer and illustrate that the CSC model can be considered an extension of the classic genetic model rather than a contradictory theory. Finally, we discuss some of the most controversial issues in this field.
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Abbreviations
- CSC:
-
cancer stem cell
- CRC:
-
colorectal cancer
- CK-20:
-
cytokeratin 20
- HSC:
-
hematopoietic stem cell
- LIC:
-
leukemia initiating cell
- GMP:
-
granulocyte–macrophage progenitor
- AML:
-
acute myeloid leukemia
- CML:
-
chronic myeloid leukemia
- ALL:
-
acute lymphoblastic leukemia
- EGF:
-
endothelial growth factor
- bFGF:
-
basic fibroblast growth factor
- TAC:
-
transit amplifying cells
- NOD/SCID:
-
non-obese diabetic/severe combined immune-deficient
- ESA:
-
epithelial-specific antigen
- ABC:
-
ATP-binding cassette
- SP:
-
side population
- MDS:
-
myelodysplastic syndromes
- CTC:
-
circulating tumor cell
- B-ALL:
-
B-cell acute lymphoblastic leukemia
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Acknowledgements
We thank Fiona C Kimberly, Monika Wolkers, Joost JC Verhoeff and Dick J Richel for careful reading of the article and useful discussion. This work was supported by a grant of the Stichting Vanderes, the AMC an EMBO Long Term Fellowship (ALTF1063-2005) (MRS) and by grants from Associazione Italiana Ricerca sul Cancro (AIRC) (GS).
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Vermeulen, L., Sprick, M., Kemper, K. et al. Cancer stem cells – old concepts, new insights. Cell Death Differ 15, 947–958 (2008). https://doi.org/10.1038/cdd.2008.20
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