A new study of mice suggests one reason for the rapid spread of glioblastoma - the most common and aggressive brain cancer in humans - is that the cancer cells hijack and feed off blood vessels in the brain, weakening the blood-brain barrier. The researchers suggest their discovery could lead to new ways to kill brain tumors that use the weakness to get targeted drugs into the brain during the early stages of the cancer.
Harald Sontheimer, Professor of Neurobiology at the University of Alabama at Birmingham, and his colleagues report the findings in the journal Nature Communications. He says they found most brain tumor cells are associated with blood vessels and:
“These cells appear to be using the vessels as highways to travel great distances within the brain.”
Glioblastoma is the most devastating and most common brain tumor in adults. According to the National Cancer Institute, there will be an estimated 23,380 new cases and 14,320 deaths from brain and other nervous system cancers in the US in 2014.
The current standard treatments for glioblastoma are chemotherapy, radiation and surgery, but even when patients receive all three their prognosis is often poor.
Blood-brain barrier is like a ‘smart’ wrapper around the brain
The blood-brain barrier is like a smart wrapper that protects the brain from foreign substances that might get into brain tissue from the bloodstream. It also ferries essential molecules to and from the brain and the bloodstream.
To this end, the blood-brain barrier has ‘tight junctions’ that form close-fitting seals between the endothelial cells of its blood vessels.
The blood vessels of the blood-brain barrier also contain astrocyte cells that have endfeet - long projections that cover 90% of their surface. The endfeet release molecules that control the tight junctions, and they also regulate blood flow in the brain by releasing other molecules that expand or contract the blood vessels.
For their study, Prof. Sontheimer and colleagues used fluorescent dyes and a variety of imaging techniques in mouse models of glioblastoma to see how tumor cells travel in the brain and how they relate to other cells and blood vessels. They focused on interactions among glioblastoma cells, astrocytes and blood vessels.
Brain tumor cells may be more vulnerable to drugs at early stage of disease
They found that outside the main tumor mass, nearly all glioblastoma cells gathered in the space between the astrocytic endfeet and the outer surface of blood vessels. It appeared that the cancer cells were using the network of small blood vessels as a scaffold to guide their migration along the blood vessels as they extracted nutrients from the blood inside.
illustration of brain tumor
Glioblastoma is the most devastating and most common brain tumor in adults.
It also appeared that the glioblastoma cells hijacked control over blood flow in the blood-brain barrier away from the astrocytes, loosening the tight junctions, and resulting in a breakdown in the barrier.
The team was astonished to find that very small groups of glioblastoma cells - even individual cells - could weaken the blood-brain barrier in the early stages of the disease.
Prof. Sontheimer says it looks like at an early stage of the disease, as they invade the blood vessels, the tumor cells are not completely protected by the blood-brain barrier. This means they could be vulnerable at this point to targeted drugs delivered via the bloodstream to the brain:
“If these findings hold true in humans, treatment with anti-invasive agents might be beneficial in newly diagnosed glioblastoma patients.”
The team says a better understanding of how tumor cells and the blood-brain barrier interact may lead to more successful ways to treat glioblastoma patients. They call for more studies to investigate how the blood-brain barrier is regulated and exactly how tumor cells hijack control over blood vessels to grow and spread.
Funds from the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, helped finance the study.
In February 2014, Medical News Today learned how biomedical engineers managed to get nanofiber “monorails” to ferry brain tumors to their death. Writing in Nature Materials, the team explained how they exploited the tendency for glioblastoma cells to spread along nerve fibers and blood vessels to lure them to potentially fatal destinations instead.
Written by Catharine Paddock PhD