Cancer Lett 2011 Dec;312 (1): 1-10. [IF:4.864]
Mesenchymal stromal cells may enhance metastasis of neuroblastoma via SDF-1/CXCR4 and SDF-1/CXCR7 signaling.
Ma M , Ye JY , Deng R , Dee CM , Chan GC .
Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, PR China.
香港大学儿科及青少年医学系，李嘉诚医学院
Abstract
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.
摘要：
高危神经母细胞瘤患者多发生骨髓转移。骨髓间质干细胞（MSCS）通过分泌基质细胞衍生因子1（SDF-1）引发肿瘤转移。本文通过研究骨髓间质干细胞作用下神经母细胞瘤细胞的转移机制，并探讨在肿瘤转移中SDF-1信号转导的作用。神经母细胞瘤表达SDF-1的受体——CXCR4和CXCR7。shRNA基因敲除表明，这些受体是导致神经母细胞瘤骨髓间充质干细胞转移的原因。CXCR4会引起神经母细胞瘤的侵袭。引起神经母细胞瘤转移的效应可以被 SDF-1受体的有效拮抗剂（AMD3100）有效地阻断。该实验研究表明，骨髓间质干细胞对抑制经分泌基质细胞衍生因子1（SDF-1）神经母细胞瘤转移起着很重要的作用，并且可以由AMD3100或shRNA敲除抑制肿瘤转移。
