Neuroblastoma cell lines display heterogeneity in differentiation responses

<ns3:p>Background Neuroblastoma is the most common extra-cranial childhood solid tumour, arising during development from stalled neural crest-derived precursor cells. In a subset of children younger than 18 months of age, neuroblastoma can undergo spontaneous regression driven by differentiation, leading to great interest in developing differentiation therapies to re-direct neuroblastoma cells down their correct developmental pathway. Recently, we have shown that combinatorial treatment with the CDK4/6 inhibitor palbociclib and differentiation-inducing agent retinoic acid inhibits proliferation and drives neuronal differentiation of adrenergic-type neuroblastoma cell lines. Methods Here, we explore the differentiation potential of neuroblastoma cell lines <ns3:italic>in vitro</ns3:italic> in response to palbociclib and retinoic acid treatment using microscopy, transcriptomic and qRT-PCR analyses. Results We present evidence suggesting that neuroblastoma cells can give rise to mixtures of neural crest-derived adrenal gland cell types, and that differentiation responses correspond to changes in patterns of extracellular matrix substrate expression. Conclusions This study builds a case to further investigate and consider heterogeneity in neuroblastoma cell differentiation and extracellular matrix changes during these cell fate decisions.</ns3:p>