Environmental cues from neural crest derivatives act as metastatic triggers in an embryonic neuroblastoma model

Dounia Ben Amar, Karine Thoinet, Benjamin Villalard, Olivier Imbaud, Clélia Costechareyre, Loraine Jarrosson, Florie Reynaud, Julia Novion Ducassou, Yohann Couté, Jean-François Brunet, Valérie Combaret, Nadège Corradini, Céline Delloye-Bourgeois () and Valérie Castellani ()
Additional contact information
Dounia Ben Amar: University of Lyon, University Claude Bernard Lyon 1, MeLiS, CNRS UMR5284, INSERM U1314, NeuroMyoGene Institute
Karine Thoinet: University of Lyon, University Claude Bernard Lyon 1, MeLiS, CNRS UMR5284, INSERM U1314, NeuroMyoGene Institute
Benjamin Villalard: University of Lyon, University Claude Bernard Lyon 1, MeLiS, CNRS UMR5284, INSERM U1314, NeuroMyoGene Institute
Olivier Imbaud: University of Lyon, University Claude Bernard Lyon 1, MeLiS, CNRS UMR5284, INSERM U1314, NeuroMyoGene Institute
Clélia Costechareyre: Oncofactory SAS, 8 avenue Rockefeller
Loraine Jarrosson: Oncofactory SAS, 8 avenue Rockefeller
Florie Reynaud: University of Lyon, University Claude Bernard Lyon 1, MeLiS, CNRS UMR5284, INSERM U1314, NeuroMyoGene Institute
Julia Novion Ducassou: University Grenoble Alpes, INSERM, CEA
Yohann Couté: University Grenoble Alpes, INSERM, CEA
Jean-François Brunet: Inserm, CNRS, École normale supérieure, PSL Research University
Valérie Combaret: Laboratory of Translational Research, Léon Bérard Centre
Nadège Corradini: Centre Léon Berard and Institut d’Hématologie et d’Oncologie Pédiatrique
Céline Delloye-Bourgeois: University of Lyon, University Claude Bernard Lyon 1, MeLiS, CNRS UMR5284, INSERM U1314, NeuroMyoGene Institute
Valérie Castellani: University of Lyon, University Claude Bernard Lyon 1, MeLiS, CNRS UMR5284, INSERM U1314, NeuroMyoGene Institute

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30237-3

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DOI: 10.1038/s41467-022-30237-3

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