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The CXCL7/CXCR1/2 axis is a key driver in the growth of clear cell renal cell carcinoma.
MedLine Citation:
PMID:  24335961     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Mutations in the VHL upregulate expression of the central angiogenic factor VEGF which drives abnormal angiogenesis in clear cell renal cell carcinomas (ccRCC). However, the overexpression of VEGF in these tumors was not found to correlate with overall survival. Here we show that the pro-angiogenic, pro-inflammatory cytokine CXCL7 is an independent prognostic factor for overall survival in this setting. CXCL7 antibodies strongly reduced the growth of ccRCC tumors in nude mice. Conversely, conditional overexpression of CXCL7 accelerated ccRCC development. CXCL7 promoted cell proliferation in vivo and in vitro, where expression of CXCL7 was induced by the central pro-inflammatory cytokine IL-1ß. ccRCC cells normally secrete low amounts of CXCL7, it was more highly expressed in tumors due high levels of IL-1ß there. We found that a pharmacological inhibitor of the CXCL7 receptors CXCR1 and CXCR2 (SB225002) was sufficient to inhibit endothelial cell proliferation and ccRCC growth. Because CXCR1 and CXCR2 are present on both endothelial and ccRCC cells, their inhibition affected both the tumor vasculature and the proliferation of tumor cells. Our results highlight the CXCL7/CXCR1/CXCR2 axis as a pertinent target for the treatment of ccRCC.
Authors:
Renaud Grepin; Melanie Guyot; Sandy Giuliano; Marina Boncompagni; Damien Ambrosetti; Emmanuel Chamorey; Jean-Yves Scoazec; Sylvie Négrier; Hélène Simonnet; Gilles Pages
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-12-12
Journal Detail:
Title:  Cancer research     Volume:  -     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-12-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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