Document Detail


Identification of the cell lineage at the origin of basal cell carcinoma.
MedLine Citation:
PMID:  20154679     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
For most types of cancers, the cell at the origin of tumour initiation is still unknown. Here, we used mouse genetics to identify cells at the origin of basal cell carcinoma (BCC), which is one of the most frequently occurring types of cancer in humans, and can result from the activation of the Hedgehog signalling pathway. Using mice conditionally expressing constitutively active Smoothened mutant (SmoM2), we activated Hedgehog signalling in different cellular compartments of the skin epidermis and determined in which compartments Hedgehog activation induces BCC formation. Activation of SmoM2 in hair follicle bulge stem cells and their transient amplifying progenies did not induce cancer formation, demonstrating that BCC does not originate from bulge stem cells, as previously thought. Using clonal analysis, we found that BCC arises from long-term resident progenitor cells of the interfollicular epidermis and the upper infundibulum. Our studies uncover the cells at the origin of BCC in mice and demonstrate that expression of differentiation markers in tumour cells is not necessarily predictive of the cancer initiating cells.
Authors:
Khalil Kass Youssef; Alexandra Van Keymeulen; Gäelle Lapouge; Benjamin Beck; Cindy Michaux; Younes Achouri; Panagiota A Sotiropoulou; Cédric Blanpain
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-14
Journal Detail:
Title:  Nature cell biology     Volume:  12     ISSN:  1476-4679     ISO Abbreviation:  Nat. Cell Biol.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-01     Completed Date:  2010-04-12     Revised Date:  2010-09-29    
Medline Journal Info:
Nlm Unique ID:  100890575     Medline TA:  Nat Cell Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  299-305     Citation Subset:  IM    
Affiliation:
Université Libre de Bruxelles (ULB), IRIBHM, Brussels B-1070, Belgium.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bacterial Proteins / genetics,  metabolism
Cadherins / metabolism
Carcinoma, Basal Cell / metabolism,  pathology*
Cell Count
Cell Differentiation
Cell Lineage*
Clone Cells / metabolism,  pathology
Ear, External / pathology
Epidermis / metabolism,  pathology*
Epithelial Cells / metabolism,  pathology
Genes, Reporter / genetics
Hair Follicle / metabolism,  pathology
Hedgehog Proteins / genetics
Integrases / genetics
Integrin beta4 / metabolism
Keratin-10 / metabolism
Keratin-14 / genetics
Keratin-15 / genetics,  metabolism
Keratin-19 / genetics
Kruppel-Like Transcription Factors / metabolism
Luminescent Proteins / genetics,  metabolism
Mice
Mice, Inbred Strains
Mice, Transgenic
Models, Biological
Neoplastic Stem Cells / metabolism,  pathology
Proteins / genetics,  metabolism
Receptors, Cell Surface / metabolism
Receptors, G-Protein-Coupled / genetics,  metabolism
Skin / metabolism,  pathology
Tail / pathology
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 0/Cadherins; 0/Gt(ROSA)26Sor protein, mouse; 0/Hedgehog Proteins; 0/Integrin beta4; 0/Keratin-14; 0/Keratin-15; 0/Keratin-19; 0/Krt1-10 protein, mouse; 0/Krt1-14 protein, mouse; 0/Krt1-15 protein, mouse; 0/Kruppel-Like Transcription Factors; 0/Luminescent Proteins; 0/Proteins; 0/Receptors, Cell Surface; 0/Receptors, G-Protein-Coupled; 0/Shh protein, mouse; 0/Smo protein, mouse; 0/patched receptors; 0/yellow fluorescent protein, Bacteria; 147785-83-9/Keratin-10; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/Integrases
Comments/Corrections
Comment In:
Cell Stem Cell. 2010 Apr 2;6(4):292-4   [PMID:  20362530 ]

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