In an initial push to explore this signaling in metastatic disease we found that ephrinB2-mediated EphB4 activation is crucial for repulsion of circulating melanoma cells from the spinal bone endothelium (Figure 5a) [7], despite previous evidence that the bone endothelium is a passive recipient of microbeads and cells alike [133]. Here, EFNB2 is linked to metastatic neoplasm.