SDF-1/CXCR4 axis promotes prostate cancer cell invasion and bone metastasis through p38, NF-κB and HIF-1α pathways

Abstract

Stromal cell-derived factor 1 (SDF-1) and its specific receptor, CXC chemokine receptor 4 (CXCR4), are associated with tumor progression and metastasis in prostate cancer (PCa). The present study aimed to explore the role of SDF-1/CXCR4-mediated metastasis of PCa cells to bone marrow, as well as the underlying molecular mechanisms. The data showed the expression of CXCR4 was significantly higher in PCa tissues than in normal prostate tissues at mRNA and protein levels (P < 0.05). CXCR4 expression was associated with vascular endothelial growth factor (VEGF) and matrix metalloprotease-9 (MMP-9) expression, and microvessel density (MVD). In vitro, SDF-1 induced cell invasion and metastasis of CXCR-positive PCa cell by increasing the expression of adhesion molecules and activation of the p38MAPK, NF-κB and HIF-1a pathways. In vivo, histopathological examinations showed SDF-1/CXCR4 axis promoted PCa progression and bone metastasis in SCID mice bearing tumor. In conclusion, CXCR4-promoted PCa progression and bone marrow trafficking were regulated by complex signaling pathways. Thus, our study lays a new foundation for targeting the SDF-1/CXCR4 axis, which could have clinical applications in inhibition of PCa progression.