Abstract
BackgroundThe 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.MethodsHuman 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.ResultsSDF-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.ConclusionOur findings support the hypothesis that ICAM-1 up-regulation stimulated by SDF-1 may play an active role in CRC cell adhesion.
Highlights
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
Effect of Stromal cell-derived factor (SDF-1) on adhesion of CRC cells to Human umbilical vein endothelial cells (HUVEC) In order to quantify the adhesion of the CRC cells to HUVECs, DLD-1 and SW48 cells were treated with different doses of SDF-1 (0–50 ng/mL) for 4 h and labeled with DiI
To assess the role of CXCR4 in SDF-1-induced cell adhesion in DLD-1 and SW48 cells, we evaluated the effect of CXCR4 inhibitor AMD3100 (100 nM) and CXCR4 neutralizing antibody on SDF-1-induced cell adhesion
Summary
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. Death due to colorectal cancer usually results from metastatic spread of cancer cells [1]. Chemokines play a pivotal role in tumor progression because they may affect growth, adhesion and metastasis of tumor cells [2,3]. (CXCL12)/Stromal cell-derived factor (SDF-1) is a member of the CXC chemokine family, which plays an important role in chemotaxis, haematopoiesis, angiogenesis and tumor spread and metastasis [4,5]. Several studies have indicated that CRC cells promoted their survival and migration to distant tissues by interaction between SDF-1 and its specific receptor, CXC receptor 4 (CXCR4). The higher expression of CXCR4 in tumor tissue correlates with poor prognosis and poor survival in CRC patients [8,9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
