Brain tumor researchers find their 'niche'January 17, 2007Demonstration by St. Jude researchers that special niches made of capillaries protect and stimulate cancer stem cells in the brain explains the origin of these cancers and their reappearance following treatment Brain tumors appear to arise from cancer stem cells (CSCs) that live within microscopic protective "niches" formed by blood vessels in the brain; and disrupting these niches is a promising strategy for eliminating the tumors and preventing them from re-growing, according to results of a study by investigators at St. Jude Children's Research Hospital. CSCs are cells that continually multiply, acting as the source of tumors. "The finding that brain CSCs exist in protective vascular (blood vessel) niches helps explain the origin of brain tumors and suggests a new strategy for eliminating them," said Richard Gilbertson, M.D., Ph.D., co-director of the Neurobiology and Brain Tumor Program at St. Jude. Gilbertson is senior author of a report on this work that appears in the January issue of Cancer Cell.
"Our data indicate that brain CSCs are nurtured by these vascular niches and that disrupting them blocks tumor growth by removing CSCs from tumors," he said. "These niches might also protect CSCs from chemotherapy drugs and irradiation therapy. So our findings could explain why aggressive tumors rapidly produce new blood vessels and why brain tumors reappear following treatment." The St. Jude team first determined that CSCs are located in vascular niches by identifying cells carrying a protein called Nestin that marks stem cells (Nestin+ cells) in four types of brain cancer removed from patients: medulloblastoma, ependymoma, oligodendroglioma and glioblastoma. They found that tumors with the densest system of tiny blood vessels contained the greatest number of Nestin+ cells, and that Nestin+ cells are located next to blood vessels in brain tumors. The investigators then examined thin sections of brain tumors and found that more than one-third of the Nestin+ cells next to blood vessels in the vascular niches had a mutation known to be linked to cancer, which suggested they were CSCs, Gilbertson said. About 30 percent of these cells were multiplying abnormally and rapidly, as expected for cancer cells. The team showed in mouse models that CSCs from brain tumors have a more natural tendency to associate closely with blood vessels than do non-CSC tumor cells. The researchers also demonstrated in test tube experiments that CSCs bind closely to cells isolated from human blood vessels. Further, the investigators found that human blood vessel cells release molecules that trigger brain CSCs to keep their identity as stem cells and continue to multiply rapidly. "This is strong evidence that the cells making up the vascular niche send signals to CSCs in the brain, causing them to grow and multiply," Gilbertson said. Gilbertson's team also studied the interaction of blood vessel cells with CSCs using mouse models of brain cancer. Mixing brain CSCs with human blood vessel cells dramatically increased the formation and growth of tumors. Brain CSCs inserted into the brain without human blood vessel cells produced tumors slowly, reaching a maximum size after seven weeks. In contrast, tumors formed by mixtures of brain CSCs and blood vessel cells grew much more rapidly, reaching a maximum growth after only four weeks. The blood vessel cells did not increase tumor growth by forming new vessels, but by associating with CSCs and stimulating these directly to produce tumors. Finally, the investigators showed that increasing the numbers of blood vessels in mouse models of brain tumors markedly increased the numbers of CSCs in tumors. The scientists also showed that drugs that deplete blood vessels from tumors inhibit tumor growth by reducing the number of CSCs. For example, the team depleted blood vessels in tumors with Avastin® (bevacizumab), an anti-angiogenic drug that blocks a protein called VEGF. Anti-angiogenic drugs block the formation of new blood vessels. "This strongly suggests that disrupting the blood vessels in brain tumors might block tumor growth by disrupting brain CSC niches," Gilbertson said. "This is important since the mechanism by which anti-angiogenic drugs, like Avastin, block tumor growth is largely unknown. Our data suggest a previously unrecognized way that anti-angiogenic agents inhibit tumor growth." The St. Jude investigators have now translated these findings into a clinical trial to determine the effectiveness of Avastin and another drug, Traceva® (erlotinib), in eliminating tumors and preventing their recurrence in children with brain cancers. St. Jude Children's Research Hospital | |||||||||||||||||||||
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Related Brain Tumor News Articles Barrow researchers identify a new approach to detect the early progression of brain tumors Researchers at Barrow Neurological Institute at St. Joseph's Hospital and Medical Center recently participated in a pilot study with the Montreal Neurological Institute that suggests a certain type of MRI scanning can detect when a patient is failing brain tumor treatment before symptoms appear. Childhood brain tumor traced to normal stem cells gone bad An aggressive childhood brain tumor known as medulloblastoma originates in normal brain "stem" cells that turn malignant when acted on by a known mutant, cancer-causing oncogene, say researchers from Dana-Farber Cancer Institute and the University of California, San Francisco (UCSF). Erectile dysfunction drugs allowed more chemotherapy to reach brain tumors in laboratory study In a study using laboratory animals, researchers found that medications commonly prescribed for erectile dysfunction opened a mechanism called the blood-brain tumor barrier and increased delivery of cancer-fighting drugs to malignant brain tumors. Certain anticancer agents could be harmful to patients with heart disease A set of promising new anticancer agents could have unforeseen risks in individuals with heart disease, suggests research at Washington University School of Medicine in St. Louis. St. Jude finds young age may give survival advantage to children with certain brain tumors St. Jude Children's Research Hospital investigators have shown that children under 3 years old who have a brain tumor called diffuse pontine glioma (DPG) appear to have a better outcome than older children with the same cancer. Brown Chemists Create Cancer-Detecting Nanoparticles A team led by a Brown University chemist has created the smallest iron oxide nanoparticles to date for cancer detection by magnetic resonance imaging (MRI). The magnetic nanoparticles operate like tiny guided missiles, seeking and attaching themselves to malignant tumor cells. Once they bind, the particles emit stronger signals that MRI scans can detect. MRI: A window to genetic properties of brain tumors Doctors diagnose and prescribe treatment for brain tumors by studying, under a microscope, tumor tissue and cell samples obtained through invasive biopsy or surgery. Protein protects embryonic stem cells' versatility and self-renewal A protein known as REST blocks the expression of a microRNA that prevents embryonic stem cells from reproducing themselves and causes them to differentiate into specific cell types, scientists at The University of Texas M. D. Anderson Cancer Center report in the journal Nature. St. Jude finds signaling system that halts the growth of a childhood brain cancer A discovery by St. Jude Children's Research Hospital scientists suggests a safer way to treat medulloblastoma, a rare but often fatal childhood brain tumor. The group found that one of the brain's signaling pathways inhibits the growth of the highly aggressive cancer cells. Paradigm shift: Switch for programmed cell death promotes spread of glioblastoma Malignant tumors have usually lost their ability to destroy themselves by programmed cell death, or apoptosis. Therefore, tumors are often resistant to chemotherapy or radiation therapy, whose effect is based on forcing tumor cells to commit suicide. More Brain Tumor News Articles |
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