CXC 趋化因子配体 12/基质细胞衍生因子-1 通过诱导细胞间黏附分子-1 调节人结肠癌细胞的细胞黏附。

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.

背景

CXC 趋化因子配体 12（CXCL12）/基质细胞衍生因子 1（SDF-1）和 CXC 受体 4（CXCR4）轴参与人类结直肠癌（CRC）的发生，并能促进 CRC 的进展。CRC 细胞与内皮细胞的相互作用是肿瘤进展的关键事件。本研究旨在探讨 SDF-1 对 CRC 细胞黏附的影响。

方法

用人 CRC DLD-1 细胞研究 SDF-1 对细胞间黏附分子 1（ICAM-1）表达和细胞与内皮黏附的影响。

结果

SDF-1 处理诱导 DLD-1 细胞黏附于内皮细胞，并增加 ICAM-1 的表达水平。小干扰 RNA（siRNA）和中和抗体抑制 ICAM-1 可抑制 SDF-1 诱导的细胞黏附。通过使用特异性抑制剂和短发夹 RNA（shRNA），我们证明 ERK、JNK 和 p38 通路的激活对于 SDF-1 诱导的 ICAM-1 表达和细胞黏附至关重要。启动子活性和转录因子 ELISA 测定表明，SDF-1 增加了 DLD-1 细胞中 Sp1、C/EBP-β 和 NF-κB-DNA 结合活性。特异性 siRNA 抑制 Sp1、C/EBP-β 和 NF-κB 激活可阻断 SDF-1 诱导的 ICAM-1 启动子活性和表达。SDF-1 对细胞黏附的影响是由 CXCR4 介导的。