Though seemingly contradictory with the notion that EphB4–ephrinB2 interaction reduces spinal metastasis formation through CTC repulsion, these results indicate that both forward and reverse signaling pathways are necessary to achieve sufficient protection from extravasation and strengthen the notion that both receptor and ligand availability need to be incorporated in future analyses of Eph–ephrin signaling in metastatic disease. The gene discussed is EPHB4; the disease is metastatic neoplasm.