Role of CX
CR1 in the adhesion and extravasation of breast cancer cells. The number of MDA-436 cells expressing exogenous CX3CR1 that were detected in the femora and tibiae of mice 24 hours after intracardiac inoculation was significantly larger than that of untransfected MDA-436 cells. The expression of the adhesion-defective Y14F mutant of the receptor failed to increase the arrival of MDA-436 cells to the skeleton, whereas the chemotaxis-defective R128N mutant was still able to promote arrival to bone similarly to the wild-type CX3CR1 (A); when animals were inspected at 72 hours post-inoculation, the difference in bone arrival between parental and CX3CR1-expressing MDA-436 cells was even more significant than what was observed after 24 hours. Also, at this later time point, cells expressing the Y14F adhesion-defective mutant were detected in numbers similar to the untrasfected cells. Finally, the cells expressing the R128N mutant, despite their ability to adhere normally to the bone marrow endothelium at 24 hours, failed to extravasate and were then detected in numbers similar to the untransfected cells (B). Between four and seven mice were used for the analysis of parental and different CX3CR1-expressing MDA-436 cells migrated to the skeleton at each time point. Data are reported as mean ± S.E.M. (*-P ≤ 0.03, **-P ≤ 0.006, ***-P < 0.0001).