- 作者: Shui-Yi Tung, Shun-Fu Chang, Ming-Hui Chou, Wen-Shih Huang, Yung-Yu Hsieh, Chien-Heng Shen, Hsing-Chun Kuo and Cheng-Nan Chen
- 作者服務機構: Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Chiayi, R.O.C.
- 中文摘要: --
- 英文摘要:
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-beta- and NF-kappaB-DNA binding activities in DLD-1 cells. Inhibition of Sp1, C/EBP-beta and NF-kappaB 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. - 中文關鍵字: --
- 英文關鍵字: Colorectal cancer, Stromal cell-derived factor-1, Intercellular adhesion molecule-1, Cell adhesion, Transcriptional regulation