Study Explains How Glioblastoma Influences Immune Cells Of Brain

Glioblastoma causes the inhibition of enzyme caspase-3 that causes the microglia to stimulate the tumor cells instead of attacking them.

Glioblastomas exert an influence on the microglia, immune cells of the brain, which causes them to stimulate cancer growth rather than attacking it. In a study published in the journal Nature Immunology, an international research team led from Sweden's Karolinska Institute explains the molecular mechanisms behind this action.

Glioblastomas are one of the most malignant forms of brain tumur and are difficult to surgically remove because the tumor cells invade the surrounding healthy brain tissue. Glioblastomas also affect the microglia - immune cells of the brain - in such a way that they stimulate the tumor cells instead of attacking them.

Glioblastoma Multiforme | Astrocytoma Grade 4 - Types, Causes, Symptoms, Diagnosis, Treatment
Glioblastomas are tumors that arise from astrocytes that make up the supportive tissue of the brain. Glioblastomas are usually highly malignant.

‘Glioma cells use a nitric oxide-dependent mechanism to force microglia, the immune cells of the brain, to modify the enzyme caspase-3 to form a tumor-stimulating form of these cells.’

The multi-national research group has previously shown that pro-inflammatory activation of microglia is controlled by a group of enzymes called caspases. In the present study, they sought to examine if the way the cancer cells affect microglia also includes similar mechanism. By cultivating microglia and glioblastoma cells together, the researchers were able to show that the cancer cells inhibit caspase-3 activity in the microglia.

"We show that it's the same inhibition of caspase-3 that causes the microglia to stimulate the tumor cells instead of attacking them," says Bertrand Joseph, Principal Investigator at Karolinska Institutet's Department of Oncology-Pathology. "When we removed caspase-3 from the microglia in a glioblastoma mouse model, the tumors grew more quickly."

According to the study authors, their results demonstrate that the glioma cells use a nitric oxide-dependent mechanism to force microglia to modify caspase-3 to form a tumor-stimulating form of these cells.

Researchers Find Keys to Glioblastoma Therapeutic Resistance
At the University of California, San Diego School of Medicine, researchers have found one of the keys to why certain glioblastomas – the primary form of a deadly brain cancer – are resistant to drug therapy.

"Two things surprised us," says Bertrand Joseph. "First and foremost, that affecting the signalling mechanism between glioblastoma cells and microglia that we discovered has such a major effect on tumor growth. Secondly, that basal caspase-3 activity, which is often considered to be an absence of activity, fulfills essential function in regulating microglia cell behavior."

A Better Prognostic Tool For Brain Cancer (Glioblastoma) Patients
A new nano-fabricated platform for observing brain cancer cells provides a much more detailed look at how the cells migrate in brain cancer patients.

Source-Medindia

Microglia Cells May Reduce Cocaine Effects
Microglia cells constantly monitor their environment, and can act to maintain normal brain functioning.