Document Detail

CXCR3/ligands are significantly involved in the tumorigenesis of basal cell carcinomas.
MedLine Citation:
PMID:  20228225     Owner:  NLM     Status:  MEDLINE    
Basal cell carcinoma (BCC) is the most common skin malignancy encountered worldwide. We hypothesized that CXC chemokines, small cytokines involved in inducing directed leukocyte chemotaxis, could play a key role in the modulation of BCC growth. In this study, quantitative RT-PCR revealed that the chemokines CXCL9, 10, 11, and their receptor CXCR3 were significantly upregulated by an average 22.6-fold, 9.2-fold, 26.6-fold, and 4.9-fold, respectively in BCC tissue samples as compared with nonlesional skin epithelium. Immunohistochemistry analysis revealed that CXCR3, CXCL10, and CXCL11, but not CXCL9, colocalized with cytokeratin 17 (K17) in BCC keratinocytes. In addition, CXCR3 and its ligands were expressed in cells of the surrounding BCC stroma. The chemokines and K17 were also expressed in cultured human immortalized HaCaT keratinocytes. Exposure of HaCaT cells or primary BCC-derived cells to CXCL11 peptides in vitro significantly increased cell proliferation. In primary BCC-derived cell cultures, addition of CXCL11 progressively selected for K17+/CXCR3+ co-expressing cells over time. The expression of CXCR3 and its ligands in human BCC keratinocytes, the enhancement of keratinocyte cell proliferation by CXCL11, and the homogeneity of K17+ BCC cells in human BCC-isolated cell population supported by CXCR3/CXCL11 signaling all suggest that CXCR3 and its ligands may be important autocrine and/or paracrine signaling mediators in the tumorigenesis of BCC.
Blanche Ka Ki Lo; Mei Yu; David Zloty; Bryce Cowan; Jerry Shapiro; Kevin John McElwee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-12
Journal Detail:
Title:  The American journal of pathology     Volume:  176     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-06     Completed Date:  2010-12-15     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2435-46     Citation Subset:  AIM; IM    
Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.
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MeSH Terms
Carcinoma, Basal Cell / metabolism*
Cell Line, Tumor
Chemokine CXCL11 / chemistry
Gene Expression Regulation, Neoplastic*
Immunohistochemistry / methods
Keratinocytes / cytology
Middle Aged
Receptors, CXCR3 / chemistry,  physiology*
Reverse Transcriptase Polymerase Chain Reaction
Skin Neoplasms / metabolism*
Grant Support
MUS-94025//Canadian Institutes of Health Research
Reg. No./Substance:
0/CXCL11 protein, human; 0/Chemokine CXCL11; 0/Ligands; 0/Receptors, CXCR3
Comment In:
Am J Pathol. 2010 May;176(5):2088-91   [PMID:  20185576 ]

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