2 min readNew Research Shows a Link between Cell Identities and Childhood Cancer Type Neuroblastoma
Solna, Sweden — Neuroblastoma often starts in the sympathetic nervous system or the adrenal glands. This cancer has a high variability in outcome, ranging from spontaneous regression and complete disappearance to relentless disease progression with very few treatment options.
The child’s age at the time of diagnosis is one of the most important prognostic factors for a favourable outcome. However, the importance of age is a question that has previously been left unanswered.
“In our research we have studied single cell sequencing in healthy adrenal tissues from fetuses, babies and older children, and compared this to tumour tissue from different neuroblastoma risk groups”, says Susanne Schlisio, associate professor at the Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet in Solna, and co-corresponding author of the study.
Different cell types with different malignancy potentials
Tumour tissue samples have been collected from children where the age at diagnosis ranged from less than a month to 6,5 years. Approximately 50 percent of the tumours were classified as high-risk and 50 percent as low-risk.
“We discovered that low-risk and high-risk neuroblastoma tumours are composed of different cell types. The different cell types also showed to have a different malignancy potential”, explains Susanne Schlisio.
The research group were able to match low-risk neuroblastoma to a cell type, which grows during the development of the fetal adrenal, while aggressive high-risk neuroblastoma matched a cell type that can only be found in children’s adrenal tissue after birth.
Analyses of these cell types also revealed different gene expression programs that control the conditions for survival in correlation with age at diagnosis. Furthermore, the study shows that the cell type found in the adrenal tissue of children after birth has the characteristics of a progenitor cell, a form of a stem cell, which can develop into specialised cell types.
“These specialised cells can help to regenerate the healthy tissue after birth, but when they become abnormal and cancerous they may also be responsible for the aggressive neuroblastoma. This would explain why high-risk neuroblastoma arises in older children, and cannot be seen in fetuses or very young babies, says Oscar Bedoya Reina, the study’s first author and assistant professor at the Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet in Solna.
Increased understanding can contribute to less malignant tumours
The researchers will now expand their study in order to understand how the identified progenitor cell type further changes after birth to create specialised cell types.
“Understanding this progenitor cell type in detail, we might be able to make predictions and preliminary validations for future therapy strategies based on tumour differentiation. Discovering pathways that can lead to childhood tumours being less malignant will be important for the development of treatments that are currently non-existent for high-risk neuroblastoma, concludes Susanne Schlisio.
Article adapted from a Karolinska Institute news release.
Publication: Single-nuclei transcriptomes from human adrenal gland reveal distinct cellular identities of low and high-risk neuroblastoma tumours. Bedoya-Reina, OC et al. Nature Communications (September 07, 2021): Click here to view.