University of Lyon, University of Lyon 1 Claude Bernard Lyon1, NeuroMyoGene Institute, CNRS UMR5310, INSERM U1217, 16 rue Raphael Dubois, F-69000 Lyon, France.
OncoFactory SAS, L'Atrium, 43 boulevard du 11 Novembre 1918, 69100 Villeurbanne, France.
Cancer Cell. 2017 Oct 9;32(4):427-443.e8. doi: 10.1016/j.ccell.2017.09.006.
Neuroblastoma (NB) is a childhood cancer arising from sympatho-adrenal neural crest cells. Disseminated forms have high frequency of multiple tumoral foci whose etiology remains unknown; NB embryonic origin limits investigations in patients and current models. We developed an avian embryonic model driving human NB tumorigenesis in tissues homologous to patients. We found that aggressive NBs display a metastatic mode, secondary dissemination via peripheral nerves and aorta. Through tumor transcriptional profiling, we found that NB dissemination is induced by the shutdown of a pro-cohesion autocrine signal, SEMA3C, which constrains the tumoral mass. Lowering SEMA3C levels shifts the balance toward detachment, triggering NB cells to collectively evade the tumor. Together with patient cohort analysis, this identifies a microenvironment-driven pro-metastatic switch for NB.
神经母细胞瘤（NB）是一种起源于交感肾上腺神经嵴细胞的儿童期癌症。播散性形式具有多个肿瘤灶的高频率，其病因仍然未知；NB 的胚胎起源限制了对患者和当前模型的研究。我们开发了一种禽类胚胎模型，可在与患者同源的组织中驱动人类 NB 肿瘤发生。我们发现侵袭性 NB 表现出转移性模式，通过外周神经和主动脉进行继发性传播。通过肿瘤转录谱分析，我们发现 NB 的传播是由一种促进黏附的自分泌信号 SEMA3C 的关闭诱导的，该信号限制了肿瘤团块。降低 SEMA3C 水平会使平衡向脱离方向倾斜，从而触发 NB 细胞集体逃避肿瘤。结合患者队列分析，这确定了一个由微环境驱动的 NB 促转移开关。
