Chemokine receptor CXCR7 assists CXCR4 in modulating the directional metastasis and EMT of pancreatic cancer / 西安交通大学学报(医学版)

ABSTRACT

Objective: To investigate the effect of CXCL12/CXCR4/CXCR7 axis on the metastasis and invasion in pancreatic cancer so as to provide new evidence for research on pancreatic cancer metastasis treatment. Methods: MiaPaCa-2 cells were transfected with CXCR4 shRNA and CXCR7 shRNA, and the Transwell assay was used to determine the effects of CXCL12/CXCR4/CXCR7 axis on cell invasion and migration. Quantitative RT-PCR and Western blotting were used to explore the effects of CXCL12/CXCR4/CXCR7 axis on the expressions of invasion-related genes (MMP-2 and uPA) and EMT-related genes (E-cadherin and Vimentin). Results: CXCL12 significantly increased the metastasis and invasion of pancreatic cancer cells. The enhancement of tumor cell invasion was effectively countered by CXCR4 shRNA or CXCR7 shRNA. CXCL12/CXCR4 axis in cancer cells increased the expressions of invasion-related genes (MMP-2 and uPA) and EMT-related genes (E-cadherin and Vimentin). CXCL12/CXCR7 axis only increased the expressions of MMP-2 and uPA. Compared to blocking CXCR4 or CXCR7 alone, the inhibitory effects on invasion-related genes and EMT-related genes were more effective when both CXCR4 and CXCR7 were blocked. Conclusion: CXCL12/CXCR4/CXCR7 axis regulates the EMT, metastasis, and invasion of pancreatic cancer cells.