Fly antimicrobial defence system doubles as tumour-killer
The identification of a new tumour-killing pathway in flies may lead to the development of new approaches to treat cancer
An antimicrobial agent called Defensin kills tumour cells and shrinks tumour size in fruit flies, with help from a pathway that flags the cells for destruction.
These findings, published in eLife, provide the first evidence in live animals that antimicrobial peptides (AMPs), which help protect against infection, also defend against cancer. If confirmed in further studies in animals and humans, the discovery could one day lead to new cancer treatment strategies.
Previous studies have shown that AMPs kill cancer cells grown in the laboratory, but the findings had not been confirmed in living creatures.
“We used the fruit fly Drosophila melanogaster to investigate whether the machinery that is best known for its role in the recognition and elimination of harmful microbes is also capable of recognising malignant cells in a living organism and eliminating them in a similar manner,” says lead author Jean-Philppe Parvy, a postdoctoral fellow at Cancer Research UK’s Beatson Institute in Glasgow.
Their experiments showed that tumour-prone fruit flies produce more Defensin than their normal counterparts. Defensin interacts with dying tumour cells in the animals. Shutting down Defensin in the tumour-prone animals leads to tumour growth, suggesting that Defensin is actively killing the cells while sparing normal cells.
Next, Parvy and his colleagues showed that Defensin recognises tumour cells in the same way it recognises harmful microbes. The fly version of a protein called Tumour Necrosis Factor helps flag the tumour cells for destruction and makes the cells more sensitive to Defensin’s attack. It does this by bringing a protein called phosphatidylserine to the surface of the tumour cells. Defensin then binds to phosphatidylserine-rich areas on the tumour cells and kills them.
“Our results reveal an anti-tumour role for Defensin in flies and provides insights on the molecular mechanisms that make tumours sensitive to the killing action of AMPs,” Parvy explains.
Further research is now needed to see if these same mechanisms are at work in mammals and humans.
“Our work may have a significant translational potential for cancer research in mammalian models as it raises the possibility that human AMPs could have anti-tumour effects similar to those of Defensin in flies,” says senior author Julia Cordero, Senior Research Fellow at the Institute of Cancer Sciences, University of Glasgow, UK. “If future work confirms this, natural AMPs or chemically designed analogues might be used in anti-cancer therapeutics.”
The paper ‘The antimicrobial peptide Defensin cooperates with Tumour Necrosis Factor to drive tumour cell death in Drosophilia’ can be freely accessed online at https:/
This work was funded by Cancer Research UK and Wellcome.
Emily Packer, Senior Press Officer
eLife is a non-profit organisation inspired by research funders and led by scientists. Our mission is to help scientists accelerate discovery by operating a platform for research communication that encourages and recognises the most responsible behaviours in science. We publish important research in all areas of the life and biomedical sciences, including Cancer Biology and Developmental Biology, which is selected and evaluated by working scientists and made freely available online without delay. eLife also invests in innovation through open-source tool development to accelerate research communication and discovery. Our work is guided by the communities we serve. eLife is supported by the Howard Hughes Medical Institute, the Max Planck Society, the Wellcome Trust and the Knut and Alice Wallenberg Foundation. Learn more at https:/
To read the latest Cancer Biology research published in eLife, visit https:/
And for the latest in Developmental Biology, see https:/
Related Journal Article