Researchers at UT Southwestern Medical Center have determined that stem cells in a certain region of the brain may be the source of a particular type of incurable brain tumor and may be implicated in other types of brain cancers as well.
The research, conducted in mice, appears in the August issue of the journal Cancer Cell. The findings support growing evidence that adult stem cells may play a role in the development of some forms of cancer, said Dr. Luis Parada, senior author on the paper and director of the Center for Developmental Biology and the Kent Waldrep Center for Basic Research on Nerve Growth and Regeneration at UT Southwestern.
"Continued research into the biology of adult stem cells will aid in the understanding of how cancers originate and develop and may lead to possible new therapies for treating aggressive, currently incurable brain tumors," said Dr. Parada.
Malignant astrocytoma, or glioma, is one of the most common types of brain tumor in adults. The tumors are thought to arise from glial cells, which are non-nerve cells that provide support and nutrition to cells of the nervous system.
Because these incurable cancers generally are not detected until they are advanced, when symptoms have begun to develop, scientists have been unsure where, or what, initiates the process of uncontrolled cell replication that leads to the formation of the tumors.
Dr. Parada and his research group, including former UT Southwestern postdoctoral researcher and lead author Dr. Yuan Zhu, now at the University of Michigan Medical School, developed a strain of genetically engineered mice that served as models for their human brain-cancer studies and allowed researchers to track down the origins of such tumors. The mice lacked a tumor suppressor gene called p53 and also had a mutated version of another tumor suppressor gene called NF1. The mutated NF1 resulted in an increase in a biochemical reaction called Ras signaling, which has been implicated in the initiation of some cancers.
As infants, the mutant mice showed no sign of cancer, but as they grew older, they all developed brain tumors. By observing and evaluating "snapshots" of changes in the mouse brains over time, Dr. Parada's research team determined that the tumors originated in neural stem cells. Those cells that became cancerous then migrated to other areas of the brain and caused tumors.
Previous research has demonstrated that adult neural stem cells are isolated in only a few regions of the mammalian brain, with the highest densities of such cells occurring in the hippocampus, an area important for learning and memory, and the subventricular zone of the forebrain.
The UT Southwestern researchers found that stem cells in the subventricular zone gave rise to malignant astrocytoma in the genetically engineered mice.