Neural crest derived progenitor cells contribute to tumor stroma and aggressiveness in stage 4/M neuroblastoma
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Pedro Linares-Clemente1,*, Diana Aguilar-Morante1,*, Ismael Rodríguez-Prieto1, Gema Ramírez3, Carmen de Torres5, Vicente Santamaría1,3, Diego Pascual-Vaca1,2, Ana Colmenero-Repiso1, Francisco M. Vega1, Jaume Mora5, Rosa Cabello4, Catalina Márquez3, Eloy Rivas2 and Ricardo Pardal1
1Instituto de Biomedicina de Sevilla (IBiS), Departamento de Fisiología Médica y Biofísica, Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Sevilla, Spain
2Departamento de Anatomía Patológica, Hospital Universitario Virgen del Rocío, Sevilla, Spain
3Departamento de Oncología Pediátrica, Hospital Universitario Virgen del Rocío, Sevilla, Spain
4Departamento de Cirugía Pediátrica, Hospital Universitario Virgen del Rocío, Sevilla, Spain
5Departamento de Oncología, Hospital Sant Joan de Déu, Barcelona, Spain
*These authors contributed equally to this work
Ricardo Pardal, email: [email protected]
Pedro Linares-Clemente, email: [email protected]
Keywords: neuroblastoma, neural crest-derived progenitors, angiogenesis, tumor stroma, smooth muscle actin (SMA)
Received: November 04, 2016 Accepted: September 04, 2017 Published: September 21, 2017
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.
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