Zebra Fish Model Yields Clues to Neuroblastoma Growth

A genome-wide association study (GWAS) conducted in a zebra fish model system identified LMO1, which encodes a LIM-domain-only transcriptional cofactor, as a neuroblastoma susceptibility gene that functions as an oncogene in high-risk neuroblastoma.

Neuroblastoma is a cancer that most commonly affects children age five years or younger, though it may rarely occur in older children. The cancer develops from immature nerve cells found in several areas of the body but most commonly arises in and around the adrenal glands, which have similar origins to nerve cells.

Investigators at the Mayo Clinic (Rochester, MN, USA) studied the mechanism used by neuroblastoma to grow and spread. They reported in the August 31, 2017, online edition of the journal Cancer Cell that genetic analyses using zebra fish demonstrated that LMO1 cooperated with the MYCN gene to accelerate tumor onset and progression.

In zebra fish expressing both MYCN and LMO1, the investigators observed tumor development in 80% of the offspring by 24 weeks of age. In offspring expressing only the MYCN gene, tumors developed in only 20 to 30% during the same time period.

The transgenic expression of LMO1 promoted neuroblastoma dissemination and distant metastasis, which was linked to cell invasion and migration, and elevated expression levels of genes affecting tumor cell-extracellular matrix interaction.

"This is the first evidence in an animal model that high levels of LMO1 expression promote metastasis of MYCN-induced neuroblastoma," said first author Dr. Shizhen Zhu, a biomedical researcher at the Mayo Clinic. "Increased expression of the LMO1 gene is associated with aggressive, high-risk neuroblastomas. Our genetic analyses using zebra fish demonstrates for the first time that LMO1 cooperates with the MYCN gene to accelerate tumor onset and increase tumor penetrance. Our zebra fish model of neuroblastoma with transgenic expression of LMO1 and MYCN should provide a valuable platform for evaluating the effects of drugs to prevent or inhibit neuroblastoma metastasis going forward."

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