Document Detail

Down-regulation of CXCL5 inhibits squamous carcinogenesis.
MedLine Citation:
PMID:  16618752     Owner:  NLM     Status:  MEDLINE    
We report a novel role for the CXC-chemokine, CXCL5, in the proliferation and invasion of head and neck squamous cell carcinoma (HNSCC). Previously, we reported transcriptional up-regulation of CXCL5 in metastatic cells. In this study, we provide biological validation of these findings and show that CXCL5 is intimately involved in tumor cell proliferation, migration, and invasion. Cells derived from a lymph node metastasis, but not from a synchronous primary tumor, secreted CXCL5 as judged by Western blotting of conditioned media. We used RNA interference to generate cell lines (shL5) in which CXCL5 expression was greatly reduced, and tested whether this modulated the cell phenotype. shL5 cells showed decreased proliferation compared with cells harboring nontargeting control sequences. In addition, we found that the ability of shL5 cells to migrate and invade in vitro through a basement membrane substitute was greatly impaired compared with control cells. Finally, whereas control cells were highly tumorigenic in nude mice, the tumorigenic potential in vivo of shL5 cells was found to be ablated. Taken together, these data suggest that CXCL5 production contributes to both enhanced proliferation and invasion of squamous cell carcinomas and that targeting of chemokine pathways may represent a potential therapeutic modality for these lesions.
Hiroshi Miyazaki; Vyomesh Patel; Huixin Wang; Ryan K Edmunds; J Silvio Gutkind; W Andrew Yeudall
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  66     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-04-18     Completed Date:  2006-06-07     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4279-84     Citation Subset:  IM    
Philips Institute, Virginia Commonwealth University, Richmond, Virginia 23298-0566, USA.
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MeSH Terms
Carcinoma, Squamous Cell / genetics,  metabolism*,  pathology*
Cell Growth Processes / physiology
Cell Line, Tumor
Cell Movement / physiology
Cell Transformation, Neoplastic / genetics,  metabolism
Chemokine CXCL5
Chemokines, CXC / antagonists & inhibitors,  biosynthesis*,  genetics
Disease Progression
Head and Neck Neoplasms / genetics,  metabolism*,  pathology*
Neoplasm Invasiveness
Neoplasm Metastasis
RNA Interference
RNA, Small Interfering / genetics
Reg. No./Substance:
0/CXCL5 protein, human; 0/Chemokine CXCL5; 0/Chemokines, CXC; 0/RNA, Small Interfering

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