title: CXC chemokine ligand 12/stromal cell-derived factor-1 regulates cell adhesion in human colon cancer cells by induction of intercellular adhesion molecule-1.
abstract: 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.
  
  
  CONCLUSIONS
  Our findings support the hypothesis that ICAM-1 up-regulation stimulated by SDF-1 may play an active role in CRC cell adhesion.
authors.affiliation: Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Shui-Yi
authors.initials: SY
authors.lastname: Tung
authors.forename: Shun-Fu
authors.initials: SF
authors.lastname: Chang
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Chou
authors.forename: Wen-Shih
authors.initials: WS
authors.lastname: Huang
authors.forename: Yung-Yu
authors.initials: YY
authors.lastname: Hsieh
authors.forename: Chien-Heng
authors.initials: CH
authors.lastname: Shen
authors.forename: Hsing-Chun
authors.initials: HC
authors.lastname: Kuo
authors.forename: Cheng-Nan
authors.initials: CN
authors.lastname: Chen
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics*; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D018799:Intercellular Adhesion Molecule-1