Neuroblastoma is a cancer that affects the sympathetic nervous system of children. It is unusual among cancers because it shows a range of outcomes: from aggressive, potentially fatal progression to a unique phenomenon where the tumor spontaneously regresses even without treatment.
Identifying why some patients regress and others don't could help thousands of patients.
A research group led by Nagoya University believes that the answer may lie in the "uncommitted" state of some neuroblastoma cells. In mice bred to have tumors that were presumed to regress, they discovered a population of "uncommitted" cells that expressed neuronal genes suggestive of a semi-differentiated state.
The findings surprised even the researchers as they suggested an entirely unknown mechanism in cancer development. "When the single-cell RNA-seq analysis first suggested the existence of uncommitted cells, I was honestly more skeptical than excited," said Shoma Tsubota from Nagoya University Graduate School of Medicine.
"Bioinformatics analyses often generate intriguing results, but experimental validation is critical," he continued. "It was only after detecting uncommitted cells through RNA in situ hybridization that we began to feel confident in our hypothesis. That was a really gratifying moment for all of us."
A further surprise followed, as when they compared their findings with human neuroblastoma datasets, they identified the same gene signatures specific to uncommitted cells in patients who had favorable outcomes.
Professor Kenji Kadomatsu, the Director of the Institute for Glyco-core Research, believes that the cells may help to identify 'oncogenic potential', which describes the tendency of cells to develop into aggressive cancer: "Although this remains speculative, we believe that uncommitted cells exhibit weaker oncogenic potential, possibly due to their intrinsic properties or the influence of their surrounding environment."
This study sheds new light on the biological basis of spontaneous regression in neuroblastoma and paves the way for future research into early diagnosis, prognosis, and the development of novel therapeutic strategies targeting early tumor cell states. The team hopes that the development of methods to specifically label or isolate uncommitted cells could enable the discovery of early diagnostic markers and novel therapeutic targets.
This research was published in the journal Neuro-Oncology, the official journal of the Society for Neuro-Oncology. The study was performed in collaboration with the Australian Children's Cancer Institute.
