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间质基质细胞可能通过 SDF-1/CXCR4 和 SDF-1/CXCR7 信号增强神经母细胞瘤的转移。

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

机构信息

Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, PR China.

出版信息

Cancer Lett. 2011 Dec 15;312(1):1-10. doi: 10.1016/j.canlet.2011.06.028. Epub 2011 Jul 7.

DOI:10.1016/j.canlet.2011.06.028
PMID:21906874
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

骨髓转移在高危神经母细胞瘤患者中经常观察到。骨髓中的间充质基质细胞(MSCs)可能通过分泌基质细胞衍生因子-1(SDF-1)来增强肿瘤转移。在这里,我们研究了 MSC 影响下神经母细胞瘤细胞的行为,并探讨了 SDF-1 信号在转移过程中的作用。神经母细胞瘤表达 SDF-1 的两种受体 CXCR4 和 CXCR7。shRNA 敲低表明这些受体负责神经母细胞瘤向 MSC 的迁移。CXCR4 还支持神经母细胞瘤的侵袭。这些作用可以通过 AMD3100(一种有效的 SDF-1 拮抗剂)有效地阻断。我们的研究表明,MSC 通过分泌 SDF-1 对神经母细胞瘤转移很重要,而 AMD3100 或 shRNA 敲低可以抑制这种作用。

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