Permissive environment required for brain tumor formation

Using a new preclinical animal model of type 1 neurofibromatosis (Nf1)-associated optic pathway tumors, researchers have found that genetic abnormalities are insufficient for brain cancer to develop.

“Brain tumors do not form in isolation,” lead investigator Dr. David H. Gutmann told Reuters Health. “The environment must also supply some chemicals or factors that promote tumor formation.”Previous findings have suggested that if a particular cell sustains enough genetic mutations, either blocking tumor suppressor gene function or amplifying an oncogene, it will become malignant, regardless of the extracellular environment.But the current research, reported in the December 15th issue of Cancer Research, suggests that finding ways to alter the external cues required to trigger tumor growth could prevent tumor growth without having to correct the underlying defect.About 20% of children with type 1 neurofibromatosis, an inherited tumor predisposition syndrome, develop low-grade pilocytic astrocytomas, primarily involving the optic nerve and chiasm, the authors explain. These tumors are characterized by biallelic inactivation of the NF1 gene. However, when Dr. Guttman’s group developed astrocyte-restricted Nf1 conditional knockout mice, the number of astrocytes in the optic nerve were increased, but astrocytomas did not develop. “So losing Nf1 is not sufficient for tumor formation,” Dr. Guttman said. Only when they crossed the conditional astrocyte Nf1 knockout mice with heterozygous Nfl mice did gliomas develop. The authors observed multiple patterns of gross pathology similar to that observed in patients with Nf1.”Something about the chemicals made by cells in surrounding brain tissue allowed the transition from increased cell growth to cancer,” Dr. Guttman said. “If we can figure out what chemicals are involved, we should have a new way to choke off cancer development.”He believes that sporadic brain tumors, arising outside of the context of Nf1, also require a brain environment that provides “fertile soil for tumor formation,” and changing that environment could alter tumor growth. (Source: Cancer Res 2003;63: Reuters Health: Karla Gale: December 16, 2003: Oncolink)