Study shows how brain tumor cells move and damage tissue, points to possible therapy

June 25, 2014 by Bob Shepard
Study shows how brain tumor cells move and damage tissue, points to possible therapy

Researchers at the University of Alabama at Birmingham have shed new light on how cells called gliomas migrate in the brain and cause devastating tumors. The findings, published June 19, 2014 in Nature Communications, show that gliomas—malignant glial cells—disrupt normal neural connections and hijack control of blood vessels.

The study provides insight into the mechanisms of how glioma cells spread throughout the as a devastating form of brain cancer, and potentially offers a tantalizing opportunity for therapy.

A hallmark of is that the cells can migrate away from a central tumor, invading healthy brain tissue. Even if a tumor mass is surgically removed, that have migrated are left behind, and can grow into a new tumor.

To grow, glioma cells need access to nutrients in the blood supply, and it is known that gliomas travel along blood vessels within the brain. Now, researchers in the lab of neuroscientist Harald Sontheimer, Ph.D., professor in the UAB Department of Neurobiology, have discovered that, as they move, gliomas dislodge astrocytic endfeet, which play a critical role in regulating blood flow in the brain.

Astrocytes are star-shaped cells in the brain that surround blood vessels and connect to them through projections called endfeet, which extend from the astrocyte and latch onto the vessel wall. The surface of nearly every blood vessel in the brain is covered by endfeet, which regulate the on the walls of blood vessels. Through that connection, instructions can be given to the to constrict the blood vessel and limit blood flow, or dilate the vessel and increase blood flow.

Sontheimer, director of the UAB Center for Glial Biology in Medicine, says that, as a person performs different neurological functions, needs to be increased to the areas responsible for that function and correspondingly decreased in other areas to maintain balance.

The arrival of a glioma cell changes all that.

"Glioma cells traveling along blood vessels literally cut the connection of astrocytic endfeet with the vessels and push them out of the way," said Sontheimer. "By disrupting this important neural connection, adverse cognitive effects could be expected. Additionally, our study showed that gliomas then take control of the blood vessels for their own ends. And those ends are primarily to obtain nutrients from blood so that they can continue to grow and spread."

Sontheimer's team says the glioma cells tend to congregate at blood vessel junctions, almost as if camping alongside a stream where it joins a river. The ready supply of nutrients would allow the cell to grow into a larger tumor mass.

By traveling on the outside of a blood vessel, glioma cells are able to access nutrients from the blood stream. As a side effect to that process, they damage the . The barrier, a layer of endothelial cells, protects the brain by restricting passage of harmful substances from the blood stream into brain tissue.

"We found that, when gliomas push away the astrocytic endfeet, damage occurs to the integrity of the that make up the blood brain barrier," said Stefanie Robel, Ph.D., a postdoctoral researcher in Sontheimer's lab and co-first author of the study. "The barrier becomes weakened, and begins to leak. A leak across the barrier can cause severe damage to ."

"That leakage appears to be a consequence of glioma cells' migrating along the blood vessels in their search for nutrients," said Stacey Watkins, an M.D./Ph.D. student in Sontheimer's lab and co-first author. "When glioma cells contact the vessels, they have direct access to nutrients."

But amid the deleterious effects that Sontheimer's team observed—shearing away the endfeet from their blood vessels, disrupting normal brain activity, hijacking control of blood vessels and causing leaks in the blood brain barrier—he says there may be a silver lining. The idea that gliomas cause the blood brain barrier to become porous and leak might open up a new avenue to kill the malignant cells as they migrate.

Chemotherapy, usually delivered intravenously, is not considered an effective strategy for killing gliomas. Chemotherapeutic agents are very effective in killing cancer elsewhere in the body, but the predominant belief is that such drugs will not pass the blood brain barrier and thus will not reach their target.

"Chemotherapy is typically not tried in cases of glioma until after other therapies such as surgery and radiation have been employed," Sontheimer said. "Our findings, which suggest that gliomas actually weaken the blood brain barrier and cause leakage, might indicate that high-dose, intravenous chemotherapy used early on following a diagnosis of brain cancer would be beneficial."

The study, funded by the National Institutes of Health and the American Brain Tumor Association, was conducted on a clinically relevant mouse model of human malignant glioma.

Sontheimer says logical next steps would be to further examine the cognitive impact of severing the astrocytic endfeet connection to .

Explore further: Researchers identify proteins that may help brain tumors spread

Related Stories

Researchers identify proteins that may help brain tumors spread

September 23, 2013
Scientists at the University of Alabama at Birmingham have identified a molecular pathway that seems to contribute to the ability of malignant glioma cells in a brain tumor to spread and invade previously healthy brain tissue. ...

Study IDs new cause of brain bleeding immediately after stroke

April 17, 2014
By discovering a new mechanism that allows blood to enter the brain immediately after a stroke, researchers at UC Irvine and the Salk Institute have opened the door to new therapies that may limit or prevent stroke-induced ...

Team moves small-molecule drugs through blood-brain barrier

June 4, 2014
Researchers at Mayo Clinic have demonstrated in a mouse model that their recently developed synthetic peptide carrier is a potential delivery vehicle for brain cancer chemotherapy drugs and other neurological medications. ...

Nano drug crosses blood-brain tumor barrier, targets brain tumor cells and blood vessels

July 17, 2013
(Phys.org) —An experimental drug in early development for aggressive brain tumors can cross the blood-brain tumor barrier and kill tumor cells and block the growth of tumor blood vessels, according to a recent study led ...

New methods to explore astrocyte effects on brain function

April 29, 2013
A study in The Journal of General Physiology presents new methods to evaluate how astrocytes contribute to brain function, paving the way for future exploration of these important brain cells at unprecedented levels of detail.

Recommended for you

Make way for hemoglobin

August 18, 2017
Every cell in the body, whether skin or muscle or brain, starts out as a generic cell that acquires its unique characteristics after undergoing a process of specialization. Nowhere is this process more dramatic than it is ...

Bio-inspired materials give boost to regenerative medicine

August 18, 2017
What if one day, we could teach our bodies to self-heal like a lizard's tail, and make severe injury or disease no more threatening than a paper cut?

Are stem cells the link between bacteria and cancer?

August 17, 2017
Gastric carcinoma is one of the most common causes of cancer-related deaths, primarily because most patients present at an advanced stage of the disease. The main cause of this cancer is the bacterium Helicobacter pylori, ...

Two-step process leads to cell immortalization and cancer

August 17, 2017
A mutation that helps make cells immortal is critical to the development of a tumor, but new research at the University of California, Berkeley suggests that becoming immortal is a more complicated process than originally ...

Female mouse embryos actively remove male reproductive systems

August 17, 2017
A protein called COUP-TFII determines whether a mouse embryo develops a male reproductive tract, according to researchers at the National Institutes of Health and their colleagues at Baylor College of Medicine, Houston. The ...

New Pathology Atlas maps genes in cancer to accelerate progress in personalized medicine

August 17, 2017
A new Pathology Atlas is launched today with an analysis of all human genes in all major cancers showing the consequence of their corresponding protein levels for overall patient survival. The difference in expression patterns ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.