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Cancer Cell. 2017 Oct 9;32(4):427-443.e8. doi: 10.1016/j.ccell.2017.09.006.

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

Author information

1
University of Lyon, University of Lyon 1 Claude Bernard Lyon1, NeuroMyoGene Institute, CNRS UMR5310, INSERM U1217, 16 rue Raphael Dubois, F-69000 Lyon, France.
2
OncoFactory SAS, L'Atrium, 43 boulevard du 11 Novembre 1918, 69100 Villeurbanne, France.
3
Drug Development Department (DITEP), Gustave Roussy Cancer Campus (GRCC), INSERM U1015, 114 rue Edouard Vaillant, 94805 Villejuif, France.
4
Laboratory of Translational Research, Léon Bérard Centre, 28 rue Laennec, 69008 Lyon, France.
5
Departments of Oncology and Clinical Research, Centre Léon Berard and Institut d'Hématologie et d'Oncologie Pédiatrique, 1 Place Professeur Joseph Renaut, 69008 Lyon, France.
6
University of Lyon, University of Lyon 1 Claude Bernard Lyon1, NeuroMyoGene Institute, CNRS UMR5310, INSERM U1217, 16 rue Raphael Dubois, F-69000 Lyon, France. Electronic address: valerie.castellani@univ-lyon1.fr.

Abstract

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.

KEYWORDS:

animal model; collective migration; embryonal cancer; metastatic switch; microenvironment; neural crest; neuroblastoma; neuroblastoma cell cohesion; plexin; semaphorin

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PMID:
29017055
DOI:
10.1016/j.ccell.2017.09.006
[Indexed for MEDLINE]
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