In the current study, Dr. Sontheimer's team showed that almost all of the glioblastoma cells outside the main tumor mass were located in the space between the astrocytic endfeet and the blood vessel outer surface. By using the meshwork of small blood vessels as a scaffold, glioblastoma cells were able to migrate along the vessels and extract nutrients from the blood for themselves.
"The vast majority of tumor cells are associated with blood vessels. These cells appear to be using the vessels as highways to travel great distances within the brain," said Dr. Sontheimer.
In addition, the findings revealed the glioblastoma cells hijacked control over the blood flow by taking it away from the astrocytes. As a result, tight junctions became loose, which led to a breakdown in the BBB. Dr. Sontheimer and his colleagues were surprised that very small groups of tumor cells, even individual cells, were sufficient to weaken the BBB early in the disease process.
"Evidence from our models suggests that early in the disease, invading tumor cells are not completely protected by the blood-brain barrier and may be more vulnerable to drugs delivered to the brain via the blood. If these findings hold true in humans, treatment with anti-invasive agents might be beneficial in newly diagnosed glioblastoma patients," said Dr. Sontheimer. He added that localized breaches in the BBB may allow regionally precise delivery of drugs to attack tumor cells even in the earliest stage.
"Dr. Sontheimer's findings provide us with new perspectives on how glioblastoma cells successfully invade within the brain and control blood flow to their advantage. These findings have the potential to change current approaches to treating glioblastoma," said Jane Fountain, Ph.D., program director in charge of NINDS' brain tumor portfolio.
|Contact: Barbara McMakin|
NIH/National Institute of Neurological Disorders and Stroke