We have previously shown that metastasis of prostate and breast cancer is in part driven by CX<sub>3</sub>CL1, and have developed small molecule inhibitors against the CX<sub>3</sub>CR1 receptor that diminish metastatic burden.
Treatment of breast cancer cells with a demethylating agent and histone deacetylase inhibitors reduced methylation of the CR-1 promoter and reactivated CR-1 mRNA and protein expression in these cells, promoting migration and invasion of breast cancer cells.
We provide compelling evidence that the functional interactions between fractalkine produced by both the endothelial and stromal cells of bone marrow and the CX₃CR1 receptor on breast cancer cells are determinant in the arrest and initial lodging needed for skeletal dissemination.