The chemokine receptor CXCR4 strongly promotes neuroblastoma primary tumour and metastatic growth, but not invasion.
The chemokine receptor CXCR4 strongly promotes neuroblastoma primary tumour and metastatic growth, but not invasion.
复制标题
DOI：
10.1371/journal.pone.0001016
复制
发表时间：
2007-10-10
期刊：
影响因子：
3.7
通讯作者：
Joseph JM
中科院分区：
文献类型：
--
作者：
Meier R;Mühlethaler-Mottet A;Flahaut M;Coulon A;Fusco C;Louache F;Auderset K;Bourloud KB;Daudigeos E;Ruegg C;Vassal G;Gross N;Joseph JM
神经母细胞瘤（NB）是一种异质性的，特别是恶性的儿童肿瘤在其较高的阶段，具有形成转移的倾向，在选定的器官，特别是肝脏和骨髓，仍然没有有效的治疗手术以外。最近的证据表明CXCR 4/CXCL 12趋化因子/受体轴可能参与促进NB的侵袭和转移。在这项研究中，我们探讨了潜在的作用CXCR 4在NB的恶性行为，在原位NB小鼠模型中使用的体外功能分析和体内生长和转移评估相结合。我们在此表明，在非转移性CXCR 4阴性NB细胞IGR-NB 8和中度转移性表达CXCR 4的NB细胞IGR-N91中，CXCR 4过表达强烈增加了原发性肿瘤和肝转移的肿瘤生长，而不改变转移的频率或模式。此外，shRNA介导的敲低实验证实了我们的观察结果，表明NB细胞中的CXCR 4沉默在体外损害并几乎消除体内生长。在小鼠肾上腺（原发肿瘤部位）和肝脏中检测到高水平的CXCL 12，表明宿主来源的CXCL 12对NB生长的旁分泌作用。总之，这项研究揭示了一个尚未报道的NB特异性的主要生长和生存促进作用的CXCR 4，这需要一个关键的重新考虑的作用，CXCR 4在NB和其他癌症的恶性行为。
Neuroblastoma (NB) is a heterogeneous, and particularly malignant childhood neoplasm in its higher stages, with a propensity to form metastasis in selected organs, in particular liver and bone marrow, and for which there is still no efficient treatment available beyond surgery. Recent evidence indicates that the CXCR4/CXCL12 chemokine/receptor axis may be involved in promoting NB invasion and metastasis. In this study, we explored the potential role of CXCR4 in the malignant behaviour of NB, using a combination of in vitro functional analyses and in vivo growth and metastasis assessment in an orthotopic NB mouse model. We show here that CXCR4 overexpression in non-metastatic CXCR4-negative NB cells IGR-NB8 and in moderately metastatic, CXCR4 expressing NB cells IGR-N91, strongly increased tumour growth of primary tumours and liver metastases, without altering the frequency or the pattern of metastasis. Moreover shRNA-mediated knock-down experiments confirmed our observations by showing that silencing CXCR4 in NB cells impairs in vitro and almost abrogates in vivo growth. High levels of CXCL12 were detected in the mouse adrenal gland (the primary tumour site), and in the liver suggesting a paracrine effect of host-derived CXCL12 on NB growth. In conclusion, this study reveals a yet unreported NB-specific predominant growth and survival-promoting role of CXCR4, which warrants a critical reconsideration of the role of CXCR4 in the malignant behaviour of NB and other cancers.
登录
查看更多内容
影响因子：
7.2
作者：
Flahaut, M;Mühlethaler-Mottet, A;Gross, N
通讯作者：
Gross, N
影响因子：
11.2
作者：
Marchesi, F;Monti, P;Allavena, P
通讯作者：
Allavena, P
影响因子：
6.7
作者：
Hasmim, M;Vassalli, G;Rüegg, C
通讯作者：
Rüegg, C
影响因子：
11.5
作者：
Airoldi, I;Raffaghello, L;Pistoia, V
通讯作者：
Pistoia, V
DOI：
10.1073/pnas.76.1.514
发表时间：
1979-01-01
影响因子：
11.1
作者：
BOTTENSTEIN, JE;SATO, GH
通讯作者：
SATO, GH