Mesenchymal stromal cells may enhance metastasis of neuroblastoma via SDF-1/CXCR4 and SDF-1/CXCR7 signaling

Bone marrow metastasis is frequently observed in patients with high-risk neuroblastoma. Mesenchymal stromal cells (MSCs) in bone marrow may enhance tumor metastasis through secreting stromal cell-derived factor-1 (SDF-1). Here we investigated neuroblastoma cell behaviors under the influence of MSCs and explored the function of SDF-1 signaling during metastasis. Neuroblastoma expressed both of the SDF-1 receptors CXCR4 and CXCR7. shRNA knockdown showed that these receptors were responsible for the migration of neuroblastoma towards MSCs. CXCR4 also supported neuroblastoma invasion. These effects could be effectively blocked by AMD3100, a potent SDF-1 antagonist. Our study suggests that MSCs are important for neuroblastoma metastasis via the secretion of SDF-1 and that such effect can be inhibited by AMD3100 or shRNA knockdown.

► Human mesenchymal stem cells (hMSCs) can enhance neuroblastoma cells migration and invasion in vitro.
► Such enhancement effect is likely to be in part contributed by the SDF-1 secreted by the hMSCs.
► SDF-1 activates the CXCR4/CXCR7 receptors of neuroblastoma cells and induces them to migrate and invade.
► Blocking of CXCR4/CXCR7 pathways can reduce the migration and invasion of neuroblastoma cells, even with MSCs support.