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

2017; Impact Journals LLC; Volume: 8; Issue: 52 Linguagem: Inglês

10.18632/oncotarget.21128

1949-2553

Pedro Linares‐Clemente, Diana Aguilar‐Morante, Ismael Rodríguez‐Prieto, Gema Ramírez, Carmen de Torres, Vicente Santa‐María, Diego Pascual-Vaca, Ana Colmenero-Repiso, Francisco M. De La Vega, Jaume Mora, R. Cabello, Catalina Márquez-Vega, Eloy Rivas, Ricardo Pardal,

Neuroblastoma Research and Treatments

// Pedro Linares-Clemente 1, * , Diana Aguilar-Morante 1, * , Ismael Rodríguez-Prieto 1 , Gema Ramírez 3 , Carmen de Torres 5 , Vicente Santamaría 1, 3 , Diego Pascual-Vaca 1, 2 , Ana Colmenero-Repiso 1 , Francisco M. Vega 1 , Jaume Mora 5 , Rosa Cabello 4 , Catalina Márquez 3 , Eloy Rivas 2 and Ricardo Pardal 1 1 Instituto de Biomedicina de Sevilla (IBiS), Departamento de Fisiología Médica y Biofísica, Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Sevilla, Spain 2 Departamento de Anatomía Patológica, Hospital Universitario Virgen del Rocío, Sevilla, Spain 3 Departamento de Oncología Pediátrica, Hospital Universitario Virgen del Rocío, Sevilla, Spain 4 Departamento de Cirugía Pediátrica, Hospital Universitario Virgen del Rocío, Sevilla, Spain 5 Departamento de Oncología, Hospital Sant Joan de Déu, Barcelona, Spain * These authors contributed equally to this work Correspondence to: Ricardo Pardal, email: rpardal@us.es Pedro Linares-Clemente, email: plinaresclemente@gmail.com 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 ABSTRACT 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.