Document Detail

Defining the mode of tumour growth by clonal analysis.
MedLine Citation:
PMID:  22854777     Owner:  NLM     Status:  MEDLINE    
Recent studies using the isolation of a subpopulation of tumour cells followed by their transplantation into immunodeficient mice provide evidence that certain tumours, including squamous skin tumours, contain cells with high clonogenic potential that have been referred to as cancer stem cells (CSCs). Until now, CSC properties have only been investigated by transplantation assays, and their existence in unperturbed tumour growth is unproven. Here we make use of clonal analysis of squamous skin tumours using genetic lineage tracing to unravel the mode of tumour growth in vivo in its native environment. To this end, we used a genetic labelling strategy that allows individual tumour cells to be marked and traced over time at different stages of tumour progression. Surprisingly, we found that the majority of labelled tumour cells in benign papilloma have only limited proliferative potential, whereas a fraction has the capacity to persist long term, giving rise to progeny that occupy a significant part of the tumour. As well as confirming the presence of two distinct proliferative cell compartments within the papilloma, mirroring the composition, hierarchy and fate behaviour of normal tissue, quantitative analysis of clonal fate data indicates that the more persistent population has stem-cell-like characteristics and cycles twice per day, whereas the second represents a slower cycling transient population that gives rise to terminally differentiated tumour cells. Such behaviour is shown to be consistent with double-labelling experiments and detailed clonal fate characteristics. By contrast, measurements of clone size and proliferative potential in invasive squamous cell carcinoma show a different pattern of behaviour, consistent with geometric expansion of a single CSC population with limited potential for terminal differentiation. This study presents the first experimental evidence for the existence of CSCs during unperturbed solid tumour growth.
Gregory Driessens; Benjamin Beck; Amélie Caauwe; Benjamin D Simons; Cédric Blanpain
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature     Volume:  488     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-23     Completed Date:  2012-09-28     Revised Date:  2014-02-24    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  527-30     Citation Subset:  IM    
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MeSH Terms
Carcinoma, Squamous Cell / genetics,  pathology
Cell Count
Cell Differentiation
Cell Lineage*
Cell Proliferation
Cell Tracking*
Clone Cells / metabolism,  pathology
Disease Models, Animal
Models, Biological
Neoplastic Stem Cells / metabolism,  pathology
Skin Neoplasms / genetics,  pathology*
Stochastic Processes
Tumor Microenvironment
Grant Support
079249//Wellcome Trust; 092096//Wellcome Trust
Comment In:
Nature. 2012 Aug 23;488(7412):462-3   [PMID:  22919708 ]
Nat Rev Clin Oncol. 2012 Oct;9(10):552   [PMID:  22889975 ]
Nat Rev Cancer. 2012 Sep;12(9):579   [PMID:  22898540 ]
Nat Methods. 2012 Oct;9(10):942-3   [PMID:  23193564 ]

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