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

• DOI: 10.1038/s41467-022-30237-3
• Publication Date: 2022-05-10T10:03:22Z
• Authors: Dounia Ben Amar; Karine Thoinet; Benjamin Villalard; Olivier Imbaud; Clélia Costechareyre; Loraine Jarrosson; Florie Reynaud; Julia Novion Duca...; Yohann Couté; Jean-François Brunet; Valérie Combaret; Nadège Corradini; Céline Delloye-Bo...; Valérie Castellani
• Keywords: Proteomics; 0301 basic medicine; 570; [SDV]Life Sciences [q-bio]; Science; Q; Cell Differentiation; Article; Neuroblastoma; 03 medical and health sciences; Neural Crest; Humans; Cues; Child

Abstract Embryonic malignant transformation is concomitant to organogenesis, often affecting multipotent and migratory progenitors. While lineage relationships between cells their physiological counterparts are extensively investigated, the contribution of exogenous embryonic signals not fully known. Neuroblastoma (NB) a childhood malignancy peripheral nervous system arising from trunk neural crest (NC) characterized by heterogeneous interconvertible tumor cell identities. Here, using experimental models mimicking context coupled proteomic transcriptomic analyses, we show that released sympathetic ganglia, including Olfactomedin-1, induce NB shift noradrenergic mesenchymal identity, activate gene program promoting metastatic onset dissemination. From this program, extract core signature specifically shared cancers with NC origin. This reveals non-cell autonomous contributions regulating plasticity identities setting pro-dissemination programs common NC-derived cancers.