Environmental cues from neural crest derivatives act as metastatic triggers in an embryonic neuroblastoma model.
Environmental cues from neural crest derivatives act as metastatic triggers in an embryonic neuroblastoma model.
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DOI：
10.1038/s41467-022-30237-3
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发表时间：
2022-05-10
影响因子：
16.6
通讯作者：
Castellani, Valerie
中科院分区：
文献类型：
--
作者：
Ben Amar, Dounia;Thoinet, Karine;Villalard, Benjamin;Imbaud, Olivier;Costechareyre, Clelia;Jarrosson, Loraine;Reynaud, Florie;Novion Ducassou, Julia;Coute, Yohann;Brunet, Jean-Francois;Combaret, Valerie;Corradini, Nadege;Delloye-Bourgeois, Celine;Castellani, Valerie
胚胎恶性转化伴随着器官发生，通常影响多能和迁移祖细胞。虽然恶性细胞和它们的生理对应物之间的谱系关系被广泛研究，但外源性胚胎信号的贡献还不完全清楚。神经母细胞瘤（NB）是一种起源于胚胎干神经嵴（NC）的儿童外周神经系统恶性肿瘤，其特征是肿瘤细胞的异质性和可相互转化。在这里，使用实验模型模拟胚胎环境耦合到蛋白质组学和转录组学分析，我们表明，胚胎交感神经节释放的信号，包括嗅介蛋白-1，诱导NB细胞从去甲肾上腺素能转移到间充质身份，并激活基因程序，促进NB转移发病和传播。从这个基因程序中，我们提取了一个与NC起源的转移性癌症特异性共享的核心签名。这揭示了非细胞自主胚胎的贡献，调节NB身份的可塑性，并设置共同的NC衍生的癌症的pro-dissemination基因程序。神经母细胞瘤的特点是细胞类型，功能间充质样或交感去甲肾上腺素能转录谱。在这里，作者表明交感神经节细胞分泌的外源性因子调节这些谱，激活促进转移过程的基因程序。
Embryonic malignant transformation is concomitant to organogenesis, often affecting multipotent and migratory progenitors. While lineage relationships between malignant cells and their physiological counterparts are extensively investigated, the contribution of exogenous embryonic signals is not fully known. Neuroblastoma (NB) is a childhood malignancy of the peripheral nervous system arising from the embryonic trunk neural crest (NC) and characterized by heterogeneous and interconvertible tumor cell identities. Here, using experimental models mimicking the embryonic context coupled to proteomic and transcriptomic analyses, we show that signals released by embryonic sympathetic ganglia, including Olfactomedin-1, induce NB cells to shift from a noradrenergic to mesenchymal identity, and to activate a gene program promoting NB metastatic onset and dissemination. From this gene program, we extract a core signature specifically shared by metastatic cancers with NC origin. This reveals non-cell autonomous embryonic contributions regulating the plasticity of NB identities and setting pro-dissemination gene programs common to NC-derived cancers. Neuroblastoma is characterised by cell types that feature mesenchymal like or sympathetic noradrenergic transcriptional profiles. Here, the authors show that exogenous factors secreted by sympathetic ganglion cells modulate these profiles, activating gene programs promoting the metastatic process.
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影响因子：
2.6
作者：
Gallik KL;Treffy RW;Nacke LM;Ahsan K;Rocha M;Green-Saxena A;Saxena A
通讯作者：
Saxena A
影响因子：
5.2
作者：
Blavier L;Yang RM;DeClerck YA
通讯作者：
DeClerck YA
DOI：
10.1126/science.aat6768
发表时间：
2018-12-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ackermann S;Cartolano M;Hero B;Welte A;Kahlert Y;Roderwieser A;Bartenhagen C;Walter E;Gecht J;Kerschke L;Volland R;Menon R;Heuckmann JM;Gartlgruber M;Hartlieb S;Henrich KO;Okonechnikov K;Altmüller J;Nürnberg P;Lefever S;de Wilde B;Sand F;Ikram F;Rosswog C;Fischer J;Theissen J;Hertwig F;Singhi AD;Simon T;Vogel W;Perner S;Krug B;Schmidt M;Rahmann S;Achter V;Lang U;Vokuhl C;Ortmann M;Büttner R;Eggert A;Speleman F;O'Sullivan RJ;Thomas RK;Berthold F;Vandesompele J;Schramm A;Westermann F;Schulte JH;Peifer M;Fischer M
通讯作者：
Fischer M
影响因子：
12.3
作者：
Cai Q;Qian X;Lang Y;Luo Y;Xu J;Pan S;Hui Y;Gou C;Cai Y;Hao M;Zhao J;Wang S;Wang Z;Zhang X;He R;Liu J;Luo L;Li Y;Wang J
通讯作者：
Wang J
影响因子：
11
作者：
Camargo, L. M.;Collura, V.;Brandon, N. J.
通讯作者：
Brandon, N. J.