Scientists have identified a Pac-Man like protein which causes cells to eat their dying neighbours, helping to prevent inflammation that can lead to cancer, a finding that may find new therapies to combat the disease.
Researchers at the University of Sheffield in the UK discovered the Rac1 protein switches cell function and causes cells to respond to ‘eat me’ signals omitted from their dying neighbouring cells and clears them away efficiently to minimise damaging inflammation.
The team, led by Nasreen Akhtar from the University’s Department of Oncology and Metabolism, made the breakthrough while studying the female breast to better understand how the organ gets rid of dead cells and surplus milk when it is no longer required.
In pregnancy, specialized epithelial cells within the breast grow to form alveoli that secrete milk.
When the milk supply is no longer required the alveoli die and the breast reverts back to a non-pregnancy state. Breast epithelia also line the mammary ducts which transport milk towards the nipple when required.
Through gene deletion studies, researchers found the Rac1 protein is crucial both for the secretion of milk and its removal in the drying-up period that follows.
Inflammatory phagocytes from the immune system are normally recruited to clear up dead cells lurking in tissues and surplus fluids.
If too many are recruited for extended periods, they can trigger inflammation within tissues, causing damage.
The study found that the breast epithelia use Rac1 to evade harmful inflammatory phagocytes from the immune system by hijacking their job.
In the first few days after weaning, live breast epithelia eat their dying neighbours and swallow all of the secretions, clearing the ducts from old milk and dead cells.
The phagocyte-like breast epithelia then die themselves and these are subsequently cleared up by professional phagocytes from the immune system.
“By doing the job themselves, the breast epithelia limit both the numbers and time of immune phagocyte infiltration which protects the tissue from becoming damaged,” Akhtar said.
“Without Rac1, the dead cells and milk flood the interconnecting breast ducts causing them to bloat and triggering chronic inflammation. The bloated ducts then fail to regenerate and produce milk in a future pregnancy,” he said.
Over 90 per cent of cancers come from epithelial cells which is why unlocking the mystery of how they work is essential.
It is fundamental to understand how healthy cells work properly in order to fully appreciate why they go wrong when cancer develops, and how best to combat the disease.
The study is published in the journal Developmental Cell.