HOW DOES PAEDIATRIC BRAIN TUMOUR SPREAD?

Edited by, SNEHA MAVIS

Medulloblastoma is a form of brain cancer that develops in the cerebellum, which is located at the back of the brain. Although rare in absolute terms approximately 350 instances are reported each year, with 60% of them involving children. Medulloblastoma is the most prevalent and lethal type of brain cancer in children. Almost all cancer fatalities are caused by metastasis to the lining of the brain or spinal cord.

Now, a study performed by USC researchers sheds fresh information on how medulloblastoma spreads to different parts of the central nervous system. The study discovered that an enzyme known as GABA transaminase, abbreviated as ABAT, helps metastases survive the hostile environment surrounding the brain and spinal cord and resist treatment.

The spread of medulloblastoma to other regions of the central nervous system is a significant challenge. Cancer cells cannot feed on the cerebrospinal fluid, which fills cavities inside the brain as well as surrounds the brain and spinal cord. The amino acid GABA makes up for what the cerebral fluid lacks in nutrition. The major function of GABA in the central nervous system is to act as a neurotransmitter in the brain and spine, reducing the effects of other messenger molecules. GABA is also broken down for energy by healthy neurons in the cerebellum. The ABAT enzyme has a role in this.

The researchers discovered that cells in the primary tumour location have lower levels of ABAT than their brain neighbors, whereas migratory medulloblastoma cells have far higher levels. In a kind of microscopic cloak-and-dagger exercise with deadly consequences, the metastases evade starvation by increasing synthesis of the ABAT enzyme, allowing them to feed on GABA.

ABAT also has the effect of slowing cell division. This turns out to be a benefit for medulloblastoma metastases, which is ironic, given that cancer is characterized by uncontrollable growth. Because radiotherapy and chemotherapy affect the body's fastest-growing cells, increased ABAT allows metastases to hide and resist treatment.

The researchers discovered that ABAT-rich tumour cells were more resistant to the chemotherapy drugs cisplatin and vincristine, which are commonly used to treat medulloblastoma cells were unable to spread to the linings of the brain and spine.