A finding from Tel Aviv University has revealed a new remarkable method that can starve a type of devastating brain tumor—glioblastoma—to death.
The study explains that glioblastoma grows in the brain because of two mechanisms. These mechanisms play significant roles in accelerating the tumor growth. The first mechanism is the one that protects cancer cells from the immune system. The second mechanism is the one that supplies energy for the tumor to develop.
The study was conducted by doctoral student Rita Perelroizen and published in the journal Brain with her supervisor, Dr. Lior Mayo of the Shmunis School of Biomedicine and Cancer Research and the Sagol School of Neuroscience, and Prof. Eytan Ruppin of the National Institutes of Health in the United States.
According to researchers, glioblastoma is a deadly brain cancer, and no potentially productive treatment can help with the cases. “The tumor cells are highly resistant to all known therapies, and, sadly, patient life expectancy has not increased significantly in the last 50 years,” they wrote.
However, the findings about the activities of these two mechanisms that accelerate the brain tumor can be a promising basis to advance the future treatments for glioblastoma and other brain tumors in general.
“Here, we tackled the challenge of glioblastoma from a new angle,” said Mayor. He explains that the study focused on the tumor’s supportive microenvironment, which are the tissues surrounding the tumor cells, instead of the tumor itself.
Specifically, the study concentrated on astrocytes (in starlike shape), a class of brain cells that are supposed to support normal brain function, which was discovered 200 years ago, and can also aggravate different brain diseases. Therefore, astrocytes may also be a double-edged knife here.
“Under the microscope we found that activated astrocytes surrounded glioblastoma tumors. Based on this observation, we set out to investigate the role of astrocytes in glioblastoma tumor growth,” according to Mayor.
To test the eradication of the tumors, the study used an animal model and started to change the activities of two mechanisms which are active around the tumors. Animals that didn’t use the treatment died within four to five weeks. On the contrary, animals with treatments ‘starving’ the glioblastoma have brought groundbreaking results. The tumor disappeared within days, leaving most animals alive without any relapse.
During mechanisms investigation, the study first came out with a research question: “How do astrocytes transform from cells that support normal brain activity into cells that support malignant tumor growth?”
The researchers proceeded to compare the genes on astrocytes between healthy brains and tumor brains. They then discovered ways to change the activities of the two mechanisms supporting tumor growth.
First, researchers changed the immune response to glioblastoma.
The study shows that there are up to 40 percent of immune cells in the tumor, mainly macrophages from the blood or brain. Astrocytes can call for a concentration of immune cells on places in the brain to prevent any events. However, these astrocytes do not play their roles in attacking the glioblastoma when they summon immune cells. On the contrary, they change the function of immune cells and support the growth of glioblastoma.
Second, investigators changed the energy in cholesterol produced in the brain that is supplied for tumor cells.
According to Mayor, the tumor grows because of its use of energy that cholesterol carries. The researchers prevented the triggers of cholesterol release into the tumor. As a result, eliminating this energy from cholesterol left the tumor dead within a few days.
“For each patient, we examined the expression levels of genes that either neutralize the immune response or provide the tumor with a cholesterol-based energy supply,” researchers state. “We found that patients with low expression of these identified genes lived longer, thus supporting the concept that the genes and processes identified are important to the survival of glioblastoma patients.”
According to Mayor, the tumor eradication tools are available in animal models but not in humans yet. However, the tumor growth is dependent on astrocytes’ activities, and the finding is giving hope in glioblastoma and brain tumor treatments in the future.