Abstract
Although the CXCL12-CXCR4/CXCR7 chemokine axis is demonstrated to play an integral role in tumor progression, the controversy exists and the role of CXCL12-CXCR4/CXCR7 signaling axis in epithelial-mesenchymal transition (EMT) of human ovarian cancer has not been explored. Here, we showed that in ovarian cancer CXCL12 induced EMT phenotypes including the spindle-like cell morphology, podia and stress fiber formation, a decrease in E-cadherin expression, and increases in mesenchymal N-cadherin and vimentin expressions. These effects of CXCL12 could be antagonized by the CXCR4 antagonist AMD3100, but not by the anti-CXCR7 antibody. The expressions of the EMT markers were significantly down-regulated by the CXCR4 siRNA, and up-regulated by the pcDNA3.1/CXCR4 plasmid, whereas not affected by the CXCR7 siRNA. Furthermore, intraperitoneal administration of AMD3100 inhibited tumor dissemination and growth in the nude mice inoculated with ovarian IGROV-1 cells with a concomitant reduction in EMT marker expressions. Collectively, these data suggest that CXCR4, rather than CXCR7, plays a key role in CXCL12-activated EMT phenotypes, and targeting the CXCL12-CXCR4 chemokine axis represents a potential therapeutic strategy to prevent ovarian cancer progression.