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Abstract
Adult stem cell niches are characterized by a dichotomy of cycling and quiescent stem cells: while the former are responsible for tissue turnover, their quiescent counterparts are thought to become active upon tissue injury thus underlying the regenerative response. Moreover, quiescence prevents adult stem cells from accumulating mutations thus ensuring a reservoir of unaltered stem cells. In the intestine, while cycling stem cells were shown to give rise to the main differentiated lineages, the identity of their quiescent equivalents remains to date elusive. This is of relevance for conditions such as Crohn's disease and ulcerative colitis where quiescent stem cells may underlie metaplasia and the increased cancer risk associated with chronic inflammation. Tumours are thought to share a comparable hierarchical structure of adult tissues with pluripotent and self-renewing cancer stem cells (CSCs) giving rise to more differentiated cellular types. As such, neoplastic lesions may encompass both cycling and quiescent CSCs. Because of their infrequent cycling, quiescent CSCs are refractory to chemo- and radiotherapy and are likely to play a role in tumour dissemination, dormancy and recurrence.
Acknowledgements
The authors are grateful to Mr. Frank van der Panne for his assistance with the artwork.
Declaration of interest: The authors declare no conflict of interest. This study was supported among others by grants from the Dutch Cancer Society, the BSIK program of the Dutch Government grant 03038 (www.stemcells.nl), and the EU FP6 and FP7 consortia Migrating Cancer Stem Cells program (MCSCs; www.mcscs.eu) and TuMIC (integrated concept of tumor metastasis (http://itgmv1.fzk.de/www/tumic/tumic_main.htm).