Mayo Clinic researchers and colleagues presented data on how neuroblastomas spread in a recent Cancer Cell paper. Specifically the study clarifies the relationship between two genes that fuel the aggressive spread of neuroblastomas.
"Increased expression of the LMO1 gene is associated with aggressive, high-risk neuroblastomas," said Shizhen Zhu, M.D., Ph.D., lead author on the paper and a biomedical researcher at Mayo Clinic. "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."
Two strains of zebra fish, developed at Mayo Clinic's Zebra Fish Facility, were engineered to express either LMO1 or MYCN at high levels. "We developed the first zebra fish model of neuroblastoma metastasis to uncover the molecular mechanism underlying LMO1-mediated neuroblastoma spread, because this is a major problem in two-thirds of the children who have high-risk disease at diagnosis," explained Dr. Zhu.
In the fish expressing both MYCN and LMO1, the authors 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.
"This is the first evidence in an animal model that high levels of LMO1 expression promote metastasis of MYCN-induced neuroblastoma," added Dr. Zhu. "The mechanism to account for this, according to our findings, is the dysregulation of genes associated with the extracellular matrix."
In zebra fish expressing both genes, markers of stiffness increased in the extracellular matrix. The authors suggest that high level of LMO1 expression changes expression of genes controlling the extracellular matrix. And that may, in turn, lead to alterations that benefit tumor growth and spread.
"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," said Dr. Zhu.