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

Shui-Yi Tung1, Shun-Fu Chang2, Ming-Hui Chou3, Wen-Shih Huang4, Yung-Yu Hsieh1, Chien-Heng Shen1, Hsing-Chun Kuo5 and Cheng-Nan Chen3*

Author Affiliations

1 Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Chiayi, Taiwan

2 Biophotonics & Molecular Imaging Research Center, National Yang Ming University, Taipei, Taiwan

3 Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan

4 Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan

5 Department of Nursing, Chang Gung University of Science and Technology; Chronic Diseases and Health Promotion Research Center, CGUST, Chiayi, Taiwan

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Journal of Biomedical Science 2012, 19:91  doi:10.1186/1423-0127-19-91

Published: 25 October 2012

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.

Conclusion

Our findings support the hypothesis that ICAM-1 up-regulation stimulated by SDF-1 may play an active role in CRC cell adhesion.

Keywords:
Colorectal cancer; Stromal cell-derived factor-1; Intercellular adhesion molecule-1; Cell adhesion; Transcriptional regulation