Influence of stromal neural crest progenitor cells on neuroblastoma radioresistance

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.

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.

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.

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.