August 12, 2015

Origins of neuroblastoma

Vanderbilt researchers are exploring how neuroblastoma tumors begin and progress, knowledge that could provide new treatments for this pediatric cancer.

Neuroblastoma – a pediatric cancer of the sympathetic (“fight or flight”) nerve ganglia and adrenal glands – is thought to originate from the cells that give rise to the developing sympathetic nervous system. Amplification of the MYCN oncogene is associated with risk in this disease, but its role in the early steps of neuroblastoma initiation is unclear.

Bret Mobley, M.D., Bruce Carter, Ph.D., and colleagues isolated sympathoadrenal progenitor cells (SAPs) – cells that generate the sympathetic nervous system – from the mouse adrenal gland.

They confirmed that the cells are multipotent, capable of generating multiple cell types. MYCN overexpression in SAPs shifted their maturation toward neurons and increased both proliferation and cell death, supporting the hypothesis that SAPs are the cells of origin for neuroblastoma. However, MYCN overexpression was not sufficient for the cells to form tumors in mice, suggesting that additional mutations are necessary for tumorigenesis.

The study, reported July 29 in PLOS ONE, presents an in vitro model system for exploring neuroblastoma initiation and progression.

This work was supported by grants from the American Cancer Society and from the National Institutes of Health (NS038220, DK061470).

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