"Is brain cancer a stem cell disease? Our study suggests that pediatric brain tumors develop from cells that have many of the same characteristics as neural stems cells, but that those cells also have an abnormal ability to grow and change. We believe that neural stem cells, found normally within our brain and spinal cords, could transform into cancer cells," said Dr. Harley Kornblum, a pediatric neurologist, member of UCLA's Jonsson Cancer Center and an associate professor of pharmacology and pediatrics at UCLA.
"We want to understand that transformation process from a normal stem cell to a cancer cell. Recent work has shown that some cancers can arise from abnormal cells that are like stem cells in that they self-renew and produce the different kinds of cells that make up a tumor. Thinking about cancer as originating from these stem cells is a new way of thinking about the fundamental nature of the disease that promises to lead to better diagnostic tests and improved cancer-specific treatments in the future," said Houman Hemmati, the lead author and an M.D./Ph.D. student in the UCLA- California Institute of Technology Medical Scientist Training Program.
The study was recently published in the online edition of the peer-reviewed journal Proceedings of the National Academy of Sciences.
"Brain tumors are notoriously difficult to treat and we are always looking for new ways to study them and new avenues for treatment," said Dr. Jorge Lazareff, director of pediatric neurosurgery and associate professor of neurosurgery at UCLA. "In children, brain tumors are the most common solid cancer. It is only by understanding the biology of these tumors that we will find a cure."
The origin of pediatric brain tumors is still unclear and scientists have wondered for some time if there is a connection between neural stem cells and brain tumors, according to Kornblum
"This study makes an important advance by demonstrating a previously unrecognized connection between stem cells and pediatric brain tumor-derived cells. By viewing tumors as a type of embryonic cell gone awry, this opens up new possibilities for diagnosis and treatment," said Dr. Marianne Bronner-Fraser, a developmental biologist and the Albert Billings Ruddock Professor of Biology at Caltech.
"It is possible that these types of cells will be the ones we want to study further and eventually attack in treating brain tumors. Additionally, the cellular mechanisms that regulate brain tumor growth may be similar to the mechanisms that regulate normal neural stem cell growth," Kornblum said. "Thus, the study of neural stem cell proliferation will provide important clues to the treatment of brain tumors. Once we know the molecules that regulate neural stem cell growth, we can use a variety of means to test whether they regulate cancer stem cell proliferation and then develop treatments to interrupt this process. Our studies also stress the importance of viewing different kinds of brain tumors as different entities in that the stem cells of origins for different tumors are different."
"This work demonstrates that major advances can be made by combining different scientific perspectives- tumor biology, stem cell and developmental biology. The joint UCLA/ Caltech program fosters this important and cross-disciplinary discovery," Bronner-Frase said.
Kornblum is the senior author of this major collaboration between UCLA and Caltech scientists and physicians, including Dr. Bronner-Fraser at Caltech and Drs. Ichiro Nakano, Daniel Geschwind and Lazareff at UCLA.
UCLA's Jonsson Comprehensive Cancer Center is composed of more than 240 cancer researchers and clinicians engaged in cancer research, prevention, detection, control and education. The center, one of the nation's largest comprehensive cancer centers, is dedicated to promoting cancer research and applying the results to clinical situations. In 2003 the center was named the best cancer center in the Western United States by U.S. News & World Report, a ranking it has held for four consecutive years.
For more information about UCLA's Jonsson Cancer Center, visit www.cancer.mednet.ucla.edu.
Journal
Proceedings of the National Academy of Sciences