CXC receptor-4 mRNA silencing abrogates CXCL12-induced migration of colorectal cancer cells

Journal of Translational Medicine

Research

Claudia Rubie¹  Otto Kollmar¹  Martin K Schilling¹  Sabrina K Faust¹  Benjamin Vicinus¹  Christoph Justinger¹  Vilma O Frick¹  Pirus Ghadjar²  Stefan Gräber³  Mathias Wagner⁴ 

[1] Department of General -, Visceral-, Vascular - and Paediatric Surgery, University of the Saarland, 66421, Homburg/Saar, Germany;Department of Radiation Oncology, Inselspital, Bern University Hospital and University of Bern, 3010, Bern, Switzerland;Institute of Medical Biometrics, Epidemiology and Medical Informatics (IMBEI), University of the Saarland, 66421, Homburg/Saar, Germany;Institute of Pathology, University of the Saarland, 66421, Homburg/Saar, Germany;

关键词: SW480 Cell;    CXCR4 Expression;    CXCL12 Expression;    CXCR4 mRNA;    CXCL12 Concentration;   

DOI  :  10.1186/1479-5876-9-22

 received in 2010-08-23, accepted in 2011-02-24,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundInteractions between CXCR4 and its ligand CXCL12 have been shown to be involved in cancer progression in colorectal cancer (CRC). We performed a comparative CXCL12/CXCR4 expression analysis and assessed the effect of external CXCL12 stimulation on migration of CRC cells without and with CXCR4 inhibition.MethodsExpression of CXCL12/CXCR4 was assessed by quantitative real-time PCR, ELISA and immunohistochemistry in resection specimens of 50 CRC patients as well as in the corresponding normal tissues and in three human CRC cell lines with different metastatic potential (Caco-2, SW480 and HT-29). Migration assays were performed after stimulation with CXCL12 and CXCR4 was inhibited by siRNA and neutralizing antibodies.ResultsIn CRC tissues CXCL12 was significantly down-regulated and CXCR4 was significantly up-regulated compared to the corresponding normal tissues. In cell lines CXCR4 was predominantly expressed in SW480 and less pronounced in HT-29 cells. CXCL12 was only detectable in Caco-2 cells. CXCL12 stimulation had no impact on Caco-2 cells but significantly increased migration of CXCR4 bearing SW480 and HT-29 cells. This effect was significantly abrogated by neutralizing anti-CXCR4 antibody as well as by CXCR4 siRNAs (P < 0.05).ConclusionsCXCR4 expression was up-regulated in CRC and CXCL12 stimulation increased migration in CXCR4 bearing cell lines. Migration was inhibited by both neutralizing CXCR4 antibodies and CXCR4 siRNAs. Thus, the expression and functionality of CXCR4 might be associated with the metastatic potential of CRC cells and CXCL12/CXCR4 interactions might therefore constitute a promising target for specific treatment interventions.

【 授权许可】

CC BY   
© Rubie et al; licensee BioMed Central Ltd. 2011