How tumors weaken blood barrier in brain cancer patients explained

Date: Jul-09-2014A 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.

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

View all articles written by Catharine, or follow her on:

Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.