Research partly funded by Neuroblastoma UK leads to an innovative stem cell model providing insight into childhood cancer origins
Fluorescently labelled mutant stem cells differentiated toward sympathetic neurons. Image recorded by Dr. Ingrid Saldana.
Researchers from the University of Sheffield and St. Anna Children’s Cancer Research Institute have created a model designed to investigate the origins of neuroblastoma, a cancer primarily affecting infants and young children. The findings offer hope for the creation of tailored treatments which treat aggressive neuroblastomas and minimise the adverse effects experienced by patients from existing therapies.
Neuroblastoma is the most common solid childhood tumour occurring outside the brain, affecting the lives of approximately 600 children in the European Union and the United Kingdom. Until now, studying genetic changes and their role in neuroblastoma initiation has been challenging due to the lack of suitable laboratory methods. A new model developed by researchers at the University of Sheffield, working closely with colleagues from the St. Anna Children's Cancer Research Institute in Vienna, replicates the emergence of early neuroblastoma cancer-like cells giving an insight into the genetic pathway of the disease.
The research, which was partly funded by Neuroblastoma UK, and published in Nature Communications, sheds light on the intricate genetic pathways which initiate neuroblastoma. An international team, led by researchers from the University of Sheffield and St. Anna Children's Cancer Research Institute in Vienna, found that specific mutations in chromosomes 17 and 1, combined with overactivation of the MYCN gene, play a pivotal role in the development of aggressive neuroblastoma tumours.
Childhood cancer is often diagnosed and detected late in the process, leaving researchers with very little idea of the conditions that led to tumour initiation, which occurs very early during foetal development. In order to understand tumour initiation, models which truthfully recreate the conditions that lead to the appearance of a tumour are needed.
The formation of neuroblastoma usually starts in the womb when a group of normal embryonic cells called ‘trunk neural crest (NC)’ become mutated and cancerous. In an interdisciplinary effort spearheaded by stem cell expert Dr. Ingrid Saldana (in Sheffield) and computational biologist Dr. Luis Montano (in Vienna), the new study found a way in which to use human stem cells to grow trunk NC cells in a petri dish. These cells carried genetic changes often seen in aggressive neuroblastoma tumours. Using genomics analysis and advanced imaging techniques, the researchers found that the altered cells started behaving like cancer cells and looked very similar to the neuroblastoma cells found in sick children.
The findings offer empowering insights and tools for the creation of tailored treatments that specifically target cancer while minimising the adverse effects experienced by patients from existing therapies.
Dr. Anestis Tsakiridis, from the University of Sheffield’s School of Biosciences and one of the lead authors of the study, said: "Our stem cell-based model mimics the early stages of neuroblastoma formation, providing invaluable insights into the genetic drivers of this devastating childhood cancer. By recreating the conditions that lead to tumour initiation, we can now explore potential treatment avenues with unprecedented precision."
Dr. Florian Halbritter, from St. Anna Children's Cancer Research Institute and second lead author of the study, adds: "This was an impressive team effort, breaching geographic and disciplinary boundaries to enable new discoveries in childhood cancer research."
