The stromal cell-derived factor-1 (SDF-1)/CXCR4 system is implicated in various instances of cell migration in mammals, including the migration of lymphocytes and the formation of
metastases. We have recently synthesized a potent novel CXCR4 antagonist,
TN14003. The purpose of this study was to investigate the role of SDF-1/CXCR4 axis in the
pancreatic cancer metastasis via cell migration and invasion, and the inhibitory effect of
TN14003 on
pancreatic cancer cell
metastasis. The expression of CXCR4 was detected in six
pancreatic cancer cell lines by Western blotting and immunocytochemistry. In migration and invasion assays, SDF-1 stimulated both migration and invasion of
cancer cells in a dose-dependent manner. The maximal effect of SDF-1 was observed at 100 ng/ml. SDF-1-induced migration and invasion of
cancer cells were completely blocked by 100 nM
TN14003. The stimulatory effect of SDF-1 on
cancer migration and the inhibitory effect of
TN14003 were mediated via the alteration in phosphorylation of
mitogen-activated protein kinases. Treatment of
cancer cells with 100 ng/ml SDF-1 resulted in a significant increase of actin polymerization, which was reduced by 100 nM
TN14003. SDF-1 enhanced
cancer cell adhesion to
laminin, which was not reversed by
TN14003. Taken together, SDF-1/CXCR4 axis is involved in
pancreatic cancer metastasis through migration and invasion. The small molecule antagonists against CXCR4 such as
TN14003 might be an effective anti-metastatic agent for
pancreatic cancer.