Neural crest derived progenitor cells contribute to tumor stroma and aggressiveness in stage 4/M neuroblastoma

Pediatric tumors arise upon oncogenic transformation of stem/progenitor cells during embryonic development. Given this scenario, the existence of non-tumorigenic stem cells included within the aberrant tumoral niche, with a potential role in tumor biology, is an intriguing and unstudied possibility. Here, we describe the presence and function of non-tumorigenic neural crest-derived progenitor cells in aggressive neuroblastoma (NB) tumors. These cells differentiate into neural crest typical mesectodermal derivatives, giving rise to tumor stroma and promoting proliferation and tumor aggressiveness. Furthermore, an analysis of gene expression profiles in stage 4/M NB revealed a neural crest stem cell (NCSC) gene signature that was associated to stromal phenotype and high probability of relapse. Thus, this NCSC gene expression signature could be used in prognosis to improve stratification of stage 4/M NB tumors. Our results might facilitate the design of new therapies by targeting NCSCs and their contribution to tumor stroma.