A recently developed mouse model of brain tumors common in the genetic disorder neurofibromatosis 1 (NF1) successfully mimics the human condition and provides unique insight into tumor development, diagnosis and treatment, according to University researchers.
After validating the model, the team made two important discoveries: New blood vessels and immune system cells may be essential to the initial formation of tumors and therefore may be promising drug targets; and brain images often used to determine the need for treatment may not be providing doctors with the information they need.
The study appeared in the January issue of the journal Annals of Neurology.
Of the two types of NF that have been identified, NF1 is among the world’s most common genetic disorders, occurring in about one out of every 3,000 births. The disorder can lead to a variety of complications, including brain cancer.
The new line of mice develops tumors along the optic nerve and optic chiasm, which transmit visual information from the eye to the brain. This type of tumor, called an optic pathway glioma, is the most common tumor in children with NF1.
The course of tumor development also is similar to that seen in humans.
They also almost always occur in children, beginning to grow before age 5 and not progressing after age 10. A similar pattern occurred in the mice.
“Tumor cell growth is dramatically reduced after a few months in mice and after a few years in humans,” said David H. Gutmann, M.D., Ph.D., the Donald O. Schnuck Family Professor of Neurology and professor of genetics and of pediatrics. “This tells us there may be growth signals early in life that are critical for tumor formation and expansion.”
Optic pathway gliomas in humans are typically surrounded by blood vessels and microglia, which are immune system cells in the brain.
The researchers found that by 3 weeks of age, the mutant mice had about four times the number of small blood vessels in the optic nerves and chiasm as control mice. Similarly, microglia were also found in these areas prior to tumor formation.
“The fact that recruitment of new blood vessels and infiltration of immune system cells occurs before actual tumor formation suggests that these events are important for the development of tumors,” Gutmann said.
“That raises the possibility that agents that can prevent the supply of growth-promoting factors provided by new blood vessels and microglia may help treat NF1 brain tumors.”
Next, researchers used the mouse model to investigate a clinical concern. Physicians rely on several tests, including MRI scans, to determine whether a child with an optic pathway glioma should undergo treatment.
The new mouse model suggests that MRI results may not correlate with tumor progression. Gutmann’s team found both growing and stable optic pathway gliomas lit up equally brightly in MRIs of the mice.
“If this finding is also true in humans, this strongly argues that MRI scans alone are not reliable tests of tumor progression,” Gutmann said.
“If we rely on them, we may be treating children with NF1 optic pathway gliomas who don’t need to be treated. Using this mouse model, we hope to hone in on more accurate diagnostic, prognostic and treatment approaches.”