Document Detail

Tumor stroma-derived Wnt5a induces differentiation of basal cell carcinoma of Ptch-mutant mice via CaMKII.
MedLine Citation:
PMID:  20233865     Owner:  NLM     Status:  MEDLINE    
Basal cell carcinoma (BCC) is the most common skin tumor in humans. Although BCCs rarely metastasize, they can cause significant morbidity due to local aggressiveness. Approximately 20% of BCCs show signs of spontaneous regression. The understanding of molecular events mediating spontaneous regression has the potential to reduce morbidity of BCC and, potentially, other tumors, if translated into tumor therapies. We show that BCCs induced in conditional Ptch(flox/flox)ERT2(+/-) knockout mice regress with time and show a more differentiated phenotype. Differentiation is accompanied by Wnt5a expression in the tumor stroma, which is first detectable at the fully developed tumor stage. Coculture experiments revealed that Wnt5a is upregulated in tumor-adjacent macrophages by soluble signals derived from BCC cells. In turn, Wnt5a induces the expression of the differentiation marker K10 in tumor cells, which is mediated by Wnt/Ca(2+) signaling in a CaMKII-dependent manner. These data support a role of stromal Wnt5a in BCC differentiation and regression, which may have important implications for development of new treatment strategies for this tumor. Taken together, our results establish BCC as an easily accessible model of tumor regression. The regression of BCC despite sustained Hedgehog signaling activity seems to be mediated by tumor-stromal interactions via Wnt5a signaling.
Frauke Nitzki; Arne Zibat; Simone K?nig; Mark Wijgerde; Albert Rosenberger; Felix H Brembeck; Per-Ole Carstens; Anke Frommhold; Anja Uhmann; Stefan Klingler; Julia Reifenberger; Tobias Pukrop; Fritz Aberger; Walter Schulz-Schaeffer; Heidi Hahn
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-16
Journal Detail:
Title:  Cancer research     Volume:  70     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-02     Completed Date:  2010-05-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2739-48     Citation Subset:  IM    
Institute of Human Genetics, University of Goettingen, Goettingen, Germany.
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MeSH Terms
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
Carcinoma, Basal Cell / genetics,  metabolism*,  pathology
Cell Differentiation / physiology
Macrophages / metabolism,  pathology
Mice, Knockout
NIH 3T3 Cells
Skin Neoplasms / genetics,  metabolism*,  pathology
Stromal Cells / metabolism,  pathology
Tamoxifen / pharmacology
Wnt Proteins / biosynthesis*,  genetics
Reg. No./Substance:
0/Wnt Proteins; 0/Wnt5a protein, mouse; 10540-29-1/Tamoxifen; EC Protein Kinase Type 2

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