CXC chemokine ligand 12/Stromal cell-derived factor-1 regulates cell adhesion in human colon cancer cells by induction of intercellular adhesion molecule-1

Background: the cxc chemokine ligand 12 (cxcl12)/stromal cell-derived factor-1 (sdf-1) and cxc receptor 4 (cxcr4) axis is involved in human colorectal cancer (crc) carcinogenesis and can promote the progression of crc. interaction between crc cells and endothelium is a key event in tumor progression. the aim of this study was to investigate the effect of sdf-1 on the adhesion of crc cells. methods: human crc dld-1 cells were used to study the effect of sdf-1 on intercellular adhesion molecule-1 (icam-1) expression and cell adhesion to endothelium. results: sdf-1 treatment induced adhesion of dld-1 cells to the endothelium and increased the expression level of the icam-1. inhibition of icam-1 by small interfering rna (sirna) and neutralizing antibody inhibited sdf-1-induced cell adhesion. by using specific inhibitors and short hairpin rna (shrna),we demonstrated that the activation of erk,jnk and p38 pathways is critical for sdf-1-induced icam-1 expression and cell adhesion. promoter activity and transcription factor elisa assays showed that sdf-1 increased sp1-,c/ebp-β- and nf-κb-dna binding activities in dld-1 cells. inhibition of sp1,c/ebp-β and nf-κb activations by specific sirna blocked the sdf-1-induced icam-1 promoter activity and expression. the effect of sdf-1 on cell adhesion was mediated by the cxcr4. conclusion: our findings support the hypothesis that icam-1 up-regulation stimulated by sdf-1 may play an active role in crc cell adhesion. © 2012 tung et al.; licensee biomed central ltd.