Tissue microenvironment modulates CXCR4 expression and tumor metastasis in neuroblastoma
Tissue microenvironment modulates CXCR4 expression and tumor metastasis in neuroblastoma
复制标题
DOI：
10.1593/neo.06670
复制
发表时间：
2007-01-01
期刊：
影响因子：
4.8
通讯作者：
Baruchel, Sylvain
中科院分区：
文献类型：
--
作者：
Zhang, Libo;Yegery, Herman;Baruchel, Sylvain
神经母细胞瘤（NB）来源于内在迁移性神经嵴细胞，具有很高的远处转移潜力。越来越多的证据表明趋化因子受体，特别是CXCR 4，通常控制免疫和炎症细胞迁移，在肿瘤进展中起重要作用。在这项研究中，我们研究了CXCR 4在8种不同的NB细胞系中的表达，发现CXCR 4的表达在NB中是动态调节的，并且可以通过不同的组织基质来调节。此外，我们证明了IL-5和IFN-γ从基质细胞中释放，并作为CXCR 4表达的差异介质。我们还在两种NB细胞系NUB-7和SK-N-BE中过表达CXCR 4（2），并在体外和体内研究了CXCR 4在NB转移中的作用。体外transwell侵袭实验表明，CXCR 4过表达促进NB细胞向骨髓基质细胞条件培养基迁移。使用体内异种移植模型，CXCR 4过表达细胞显示转移的发生率增加，最显著的是骨髓转移。我们的研究揭示了CXCR 4在NB转移中的关键作用，并为NB中趋化因子受体的调节机制以及组织微环境在调节肿瘤细胞行为中的重要性提供了见解。
Neuroblastoma (NB) is derived from intrinsic migratory neural crest cells and has a high potential for distant metastasis. Growing evidence has implicated chemokine receptors, especially CXCR4, which normally control immune and inflammatory cell migration, as having important roles in tumor progression. In this study, we investigated the expression of CXCR4 in eight different NB cell lines and found that CXCR4 expression is dynamically regulated in NB and can be modulated by different tissue stromata. In addition, we demonstrate that IL-5 and IFN-gamma are released from stromal cells and act as differential mediators for CXCR4 expression. We also overexpressed CXCR4 in two NB cell lines, NUB-7 and SK-N-BE(2), and studied the role of CXCR4 in NB metastasis both in vitro and in vivo. In vitro transwell invasion assay showed that CXCR4 overexpression promoted NB cell migration preferentially toward a bone marrow stromal cell-conditioned medium. Using an in vivo xenograft model, CXCR4-overexpressing cells showed an increased incidence of metastasis, most notably bone marrow metastasis. Our studies reveal critical roles for CXCR4 in NB metastasis and provide insights into the regulatory mechanism of chemokine receptors in NB and the importance of the tissue microenvironment in modulating tumor cell behavior.