Microenvironment-Driven Shift of Cohesion/Detachment Balance within Tumors Induces a Switch toward Metastasis in Neuroblastoma

Céline Delloye-Bourgeois; Lorette Bertin; Karine Thoinet; Loraine Jarrosson; Karine Kindbeiter; Thomas Buffet; Servane Tauszig-Delamasure; Muriel Bozon; Aurélien Marabelle; Valérie Combaret; Christophe Bergeron; Edmund Derrington; Valérie Castellani

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Microenvironment-Driven Shift of Cohesion/Detachment Balance within Tumors Induces a Switch toward Metastasis in Neuroblastoma

机译：微环境驱动的肿瘤内的内聚力/脱离平衡的转移诱导神经母细胞瘤中转移的切换

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Summary 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. Graphical Abstract Display Omitted Highlights ? We set an animal model fully replicating human NB tumorigenesis and dissemination ? Stage 4 NB foci arise from metastatic dissemination via peripheral nerves and aorta ? RNA-seq data reveal an NB gene program regulated by the embryonic microenvironment ? Sema3C signaling shutdown in NB primary tumors is a master pro-metastatic trigger Delloye-Bourgeois et?al. developed an aggressive human neuroblastoma (NB) model in which NB cells disseminate via peripheral nerves and aorta by placing the cells at their primitive environment in avian embryos. NB dissemination is regulated by a cohesion signaling controlled by SEMA3C via NRP/PLXN complexes.

机译：发明内容神经母细胞瘤（NB）是来自同情肾上腺神经嵴细胞产生的儿童癌症。传播形式具有高频率的多个肿瘤灶，其病因仍然未知; NB胚胎来源限制患者和当前模型的研究。我们开发了一种禽流胚模型，在对患者同源组织中驾驶人NB肿瘤内核。我们发现激进的NBS显示转移模式，通过外周神经和主动脉进行二次播种。通过肿瘤转录分析，我们发现通过关闭促致肿瘤质量的亲凝聚性自分泌信号，SEMA3C诱导Nb传播。降低SEMA3C水平将平衡转移到脱离，触发NB细胞共同避免肿瘤。与患者队列分析一起，这识别了用于NB的微环境驱动的Pro-MetaTyatic开关。图形抽象显示省略了亮点？我们将动物模型完全复制人类Nb肿瘤引发和传播？第4阶段Nb病灶来自通过外周神经和主动脉的转移性散发？ RNA-SEQ数据显示由胚胎微环境调节的Nb基因计划？ Nb原发性肿瘤中的SEMA3C信号关断是Master Pro-Meta触发Delloye-Bourgeois等。开发了一种积极的人神经母细胞瘤（Nb）模型，其中Nb细胞通过将细胞放置在禽胚胎中的原始环境中通过外周神经和主动脉散发。 Nb传播由通过NRP / PLXN配合物控制的SEMA3C控制的凝聚力信号调节。

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来源
《Cancer Cell》 |2017年第4期|共17页
作者
Céline Delloye-Bourgeois; Lorette Bertin; Karine Thoinet; Loraine Jarrosson; Karine Kindbeiter; Thomas Buffet; Servane Tauszig-Delamasure; Muriel Bozon; Aurélien Marabelle; Valérie Combaret; Christophe Bergeron; Edmund Derrington; Valérie Castellani;
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作者单位

University of Lyon University of Lyon 1 Claude Bernard Lyon1 NeuroMyoGene Institute CNRS UMR5310;

University of Lyon University of Lyon 1 Claude Bernard Lyon1 NeuroMyoGene Institute CNRS UMR5310;

University of Lyon University of Lyon 1 Claude Bernard Lyon1 NeuroMyoGene Institute CNRS UMR5310;

OncoFactory SAS L'Atrium;

University of Lyon University of Lyon 1 Claude Bernard Lyon1 NeuroMyoGene Institute CNRS UMR5310;

University of Lyon University of Lyon 1 Claude Bernard Lyon1 NeuroMyoGene Institute CNRS UMR5310;

University of Lyon University of Lyon 1 Claude Bernard Lyon1 NeuroMyoGene Institute CNRS UMR5310;

University of Lyon University of Lyon 1 Claude Bernard Lyon1 NeuroMyoGene Institute CNRS UMR5310;

Drug Development Department (DITEP) Gustave Roussy Cancer Campus (GRCC) INSERM U1015;

Laboratory of Translational Research Léon Bérard Centre;

Departments of Oncology and Clinical Research Centre Léon Berard and Institut d'Hématologie et d;

University of Lyon University of Lyon 1 Claude Bernard Lyon1 NeuroMyoGene Institute CNRS UMR5310;

University of Lyon University of Lyon 1 Claude Bernard Lyon1 NeuroMyoGene Institute CNRS UMR5310;

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原文格式 PDF
正文语种 eng
中图分类肿瘤学;
关键词
animal model; embryonal cancer; neuroblastoma; microenvironment; neural crest; collective migration; neuroblastoma cell cohesion; metastatic switch; semaphorin; plexin;

机译：动物模型;胚胎癌;神经母细胞瘤;微环境;神经嵴;集体迁移;神经母细胞瘤细胞内聚力;转移开关;信号素;丛林;

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1. Microenvironment-Driven Shift of Cohesion/Detachment Balance within Tumors Induces a Switch toward Metastasis in Neuroblastoma [J] . Céline Delloye-Bourgeois, Lorette Bertin, Karine Thoinet, Cancer Cell . 2017,第4期

机译：微环境驱动的肿瘤内的内聚力/脱离平衡的转移诱导神经母细胞瘤中转移的切换
2. Multicolor fluorescence-based approaches for imaging cytokine-induced alterations in the neovascularization, growth, metastasis, and apoptosis of murine neuroblastoma tumors. [J] . Stauffer JK, Khan T, Salcedo R, Journal of immunotherapy . 2006,第2期

机译：基于多色荧光的方法，对小鼠神经母细胞瘤肿瘤的新血管形成，生长，转移和凋亡中的细胞因子诱导的变化进行成像。
3. ITIH5 induces a shift in TGF-beta superfamily signaling involving Endoglin and reduces risk for breast cancer metastasis and tumor death [J] . Rose Michael, Meurer Steffen K., Kloten Vera, Molecular Carcinogenesis . 2018,第2期

机译：ITIH5诱导TGF-Beta超家族信号传导的转变，涉及胚胎林，降低乳腺癌转移和肿瘤死亡的风险
4. Exploring Baseline Shift Prediction in Respiration Induced Tumor Motion [C] . Balasubramanian Arvind, Shamsuddin Rittika, Yam Cheung, IEEE International Conference on Healthcare Informatics . 2014

机译：探索呼吸诱发的肿瘤运动中的基线偏移预测
5. The role of VEGF autocrine signaling in hypoxia and oxidative stress driven "stemness switch": Implications in solid tumor progression and metastasis. [D] . Das, Bikul. 2007

机译：VEGF自分泌信号在缺氧和氧化应激驱动的“茎干转换”中的作用：对实体瘤进展和转移的影响。
6. Molecular Pathways in Cell Signaling: Detachment-induced E-cadherin expression promotes 3D tumor spheroid formation but inhibits tumor formation and metastasis of lung cancer cells [O] . Phattrakorn Powan, Sudjit Luanpitpong, Xiaoqing He, -1

机译：细胞信号传导中的分子途径：分离诱导的E-钙黏着蛋白表达促进3D肿瘤球体形成但抑制肿瘤细胞的形成和转移。
7. A new tumorsphere culture condition restores potentials of self-renewal and metastasis of primary neuroblastoma in a mouse neuroblastoma model. [O] . Dongliang Cao, Satoshi Kishida, Peng Huang, 2014

机译：新的肿瘤球体培养条件恢复了小鼠神经母细胞瘤模型中原发性神经母细胞瘤的自我更新和转移的潜力。
8. All-Optical Switching Based on Induced Wavelength Shift in a CDSSE-Doped Fiber [R] . Donkor, E. 1997

机译：基于CDssE掺杂光纤中感应波长漂移的全光开关

Microenvironment-Driven Shift of Cohesion/Detachment Balance within Tumors Induces a Switch toward Metastasis in Neuroblastoma

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