Science & Technology, UK (Commonwealth Union) – Scientists from the University College London (UCL) Cancer Institute have given a significant molecular understanding of the way injury may impact the formation of a relatively rare but often aggressive form of brain tumor known as glioma.
Glioma is a type of tumor that originates in the brain and spinal cord. It is a type of cancer that develops from glial cells, which are cells that provide support and protection to the nerve cells in the central nervous system. Gliomas can be either benign or malignant, and can occur at any age, although they are more common in adults.
Prior research pointed in the direction of a possible connection between head injury and elevated rates of brain tumors, however the evidence is inconclusive.
UCL researchers have currently identified a potential mechanism to shed light on this association, implicating genetic mutations that act in concert with brain tissue inflammation altering the behavior of cells, increasing their chance of becoming cancerous.
In spite the research being conducted in mice, the scientists indicate that it would be significant to look into the relevance of these results in human gliomas.
The study was led by Professor Simona Parrinello of the UCL Cancer Institute, Head of the Samantha Dickson Brain Cancer Unit as well as co-lead of the Cancer Research UK Brain Tumour Centre of Excellence. Professor Simona Parrinello says “Our research suggests that a brain trauma may contribute to an increased risk of developing brain cancer in later life.”
Gliomas regularly arise in neural stem cells, where the more mature types of brain cells, like astrocytes, have been considered to have a reduced chance of leading to tumors. But recent findings showed that following injury astrocytes could demonstrate stem cell behavior again.
Professor Parrinello and her researchers embarked on an investigation to find out if this property may make astrocytes capable of forming a tumor after brain trauma with the application of a pre-clinical mouse model.
The young adult mice who had brain injury were injected with a substance that permanently marked astrocytes in red and knocked out the function of the p53 gen, known to have a significant part in blocking a lot of different cancers. A control group was conducted in the same manner, however the p53 gene was kept intact. A 2nd group of mice has their p53 inactivated with no injury.
Professor Parrinello says “Normally astrocytes are highly branched – they take their name from stars – but what we found was that without p53 and only after an injury the astrocytes had retracted their branches and become more rounded. They weren’t quite stem cell-like, but something had changed. So we let the mice age, then looked at the cells again and saw that they had completely reverted to a stem-like state with markers of early glioma cells that could divide.”.
These indicated to Professor Parrinello and the researchers that mutations in some genes synergized with brain inflammation, this is induced by acute injury and then elevated over time as the natural process of ageing takes place to give astrocytes an increased chance to start a cancer. Indeed, this method of alteration to stem-cell like behavior increased when they injected mice having a solution known to result in inflammation as indicated by researchers.
The team then looked for evidence to back their hypothesis in human populations. Engaging with Dr Alvina Lai in the UCL Institute of Health Informatics, they used electronic medical records of more than 20,000 individuals who were diagnosed with head injuries, contrasting the rate of brain cancer with a control group, matching demographics like age, sex and socioeconomic status.
It was discovered that patients having a head injury were nearly 4 times more likely to form a brain cancer later in life, compared with those with no head injury.
