Researchers from the University of Illinois Cancer Center discovered that neuroblastoma cancer cells can be induced to become non-malignant by placing the cells in specific locations in the developing zebrafish or mouse embryo. The finding offers new insights into the most common and devastating solid tumor in infants.
Neuroblastoma is a rare childhood cancer that is thought to develop from immature nerve cells, known as neuroblasts. Neuroblastoma is often found in the small glands on top of the kidneys, called adrenal glands.
It can develop or spread in the stomach, chest, neck, pelvis, and bones but is rarely found in the head. Children ages five or younger are most commonly affected. The overall five-year survival rate for neuroblastoma is 81%, which drops to 50% for children with high-risk disease.
The research team, including University of Illinois Chicago medical and graduate students, sought to understand why neuroblastoma develops mainly in the trunk of the body, said lead author and Cancer Center member Ankur Saxena, Ph.D. They transplanted human neuroblastoma cells into streams of neural crest stem cells in live zebrafish and mouse embryos. The cancer cells were then co-transported towards the head or body.
The findings, published in Developmental Cell, demonstrate that neuroblastoma cells react to their physical location in the developing vertebrate embryo, with certain environments allowing survival while others do not. The discovery that human neuroblastoma cells, including patient-derived xenografts, are sensitive to this anatomical context could have major implications for the development of new treatments.
“Remarkably, most neuroblastoma cells that hitched a ride into the developing head differentiated and died. But outside of that environment, they continued to proliferate and survive, as one would expect of cancer cells,” Dr. Saxena said. “Our findings suggest that microenvironmental signaling has a previously unappreciated capacity to halt these early malignancies, which may speak to neuroblastoma’s localization in patients.”
The study also pinpointed several signaling molecules, including retinoic acid and brain-derived neurotrophic factor, which are required for neuroblastoma differentiation.