NB cells cultured as spheroids have been shown to better mimic the growth characteristics of in vivo solid tumors.[11, 14] However, this spheroid model alone cannot fully exhibit the complexity of the TME which integrates multiple other cellular components including ECs, as well as the tissue ECM, which has been shown to modulate both chemotherapy response and expression of key oncogenes relevant to NB such as MYCN. This evidence concerns the gene MYCN and neuroblastoma.