Influence of stromal neural crest progenitor cells on neuroblastoma radioresistance

Purpose A substantial proportion of children with high risk Neuroblastoma die within the first 5 years post-diagnosis despite the complex treatment applied. In the recent years, tumor environment has been revealed as key factor for cancer treatment efficacy. In this sense, non-tumorigenic Neural Cre...

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Detalles Bibliográficos
Autores: Huertas Castaño, Carlos, Martínez López, Laura, Cabrera Roldán, Patricia, Pastor Carrillo, Nuria María, Mateos Pérez, Juan Carlos, Mateos Cordero, Santiago, Pardal Redondo, Ricardo, Domínguez García, Inmaculada, Orta Vázquez, Manuel Luis
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2025
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/180844
Acceso en línea:https://hdl.handle.net/11441/180844
https://doi.org/10.1080/09553002.2024.2440865
Access Level:acceso abierto
Palabra clave:DNA Repair
Radiotherapy
Neuroblastoma
Stroma
Descripción
Sumario:Purpose A substantial proportion of children with high risk Neuroblastoma die within the first 5 years post-diagnosis despite the complex treatment applied. In the recent years, tumor environment has been revealed as key factor for cancer treatment efficacy. In this sense, non-tumorigenic Neural Crest progenitor cells from high risk patients, have been described as part of Neuroblastoma stroma, promoting tumor growth and contributing to mesenchyme formation. In this paper we wanted to study the radiobiological behavior of these cells (NB14t) and how they influence the growth of tumorigenic neuroblasts after radiotherapy. Materials and methods To achieve our aim, we employed a wide list of methods either using NB14t cells as well as commercial NB cells. We have analyzed viability, survival, cell cyle profiles and differentiation. In addition, cocultured experiments were performed to monitor the influence of stroma cells to tumorigenic neuroblasts. Results We found that stromal progenitor cells showed an extraordinary radio-resistance either cultured in attached or suspension conditions. In good agreement, we found an enhanced repair of irradiation-induced DNA lesions as compared with commercial cell lines. In addition, according to our data these cells differentiate into a Cancer Associated Fibroblasts (CAFs)-like phenotype, hence contributing to the formation of mesenchymal stroma enhancing the growth of tumor cells after irradiation. Conclusion Our data show that neural progenitor cells from high risk NB stroma are radio-resistant and promote cancer growth after irradiation. This paper can help to understand the complex cell relationships within a tumor that will determine patient prognosis after radiotherapy.