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.

中文翻译：

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肿瘤内微环境驱动的内聚力/迁移平衡的转移诱导了向神经母细胞瘤转移的转变。

神经母细胞瘤（NB）是由交感肾上腺神经rest细胞引起的儿童期癌症。散发的形式具有多个病灶的高频率，其病因尚不清楚。NB胚胎起源限制了对患者和当前模型的研究。我们开发了一种在与患者同源的组织中驱动人NB肿瘤发生的禽类胚胎模型。我们发现，侵袭性的NBs表现出转移模式，通过周围神经和主动脉的继发性传播。通过肿瘤转录谱，我们发现NB的传播是由前凝聚自分泌信号SEMA3C的关闭引起的，后者抑制了肿瘤块。降低SEMA3C水平会使平衡朝着分离方向移动，从而触发NB细胞共同逃避肿瘤。连同患者队列分析，