The role of CXCL12/CXCR4 axis in interaction between pancreatic cancer and neural cells

Objective: To illustrate the role and possible molecular mechanism of CXCL12/CXCR4 axis in the interaction between pancreatic cancer and neural cells. Methods: Different pancreatic cancer cells (Panc-1 and Miapaca-2) cultured in vitro were harvested and divided into CXCL12 group, AMD3100 group (CXCR4 antagonist) and control group. RT-PCR was applied to investigate the mRNA expressions of CXCR4, CXL12, matrix metalloproteinases (MMPs) and human urokinase plasminogen activator (uPA). Transwell invasion assay was applied to analyze the invasive ability of tumor cells in different groups. Co-culture between tumor cells and dorsal root ganglia (DRG) cells was applied to analyze the perineural invasion (PNI) of pancreatic cancer in different groups. Results: The mRNA expression of CXCR4 was observed in pancreatic cancer cells and DRG, but CXCL12 was found only in DRG cells. CXCL12 significantly increased the expressions of MMP-2, MMP-9 and uPA (P<0.01) in pancreatic cancer cells, which could strengthen the invasive ability of pancreatic caner; however, CXCR4 antagonist AMD3100 could inhibit the phenomenon. CXCL12 group, CXCR4 antagonists group and control group differed significantly (P<0.05). Co-culture study showed that more growth of axon and PNI was observed in CXCL12 group than in control group (P<0.05). Additionally, AMD3100 inhibited the growth of axon and PNI. Conclusion: CXCLl2/CXCR4 axis can increase the invasive ability of pancreatic cancer cells and induce neural invasion of pancreatic cancers. Additionally, CXCL12 derived from neural cells and Schwann cells may cause the CXCR4 positive pancreatic cancer cells to move toward the neural cells, inducing neural infiltration.