Fly antimicrobial defence system doubles as tumour-killer

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Fly antimicrobial defence system doubles as tumour-killer

An antimicrobial agent called Defensin kills tumor cells and reduces tumor size in fruit flies, using a pathway that marks cells for destruction.

These results, published in eLife, provide the first evidence in live animals that antimicrobial peptides (AMPS), which help protect against infections, also protect against cancer. If confirmed by further studies in animals and humans, this discovery may one day lead to new cancer treatment strategies.

Previous studies have shown that MPAs kill laboratory-cultured cancer cells, but the results have not been confirmed in living organisms.

"We have used the fruit fly Drosophila melanogaster to determine whether the machine best known for its role in recognizing and eliminating harmful microbes is also able to recognize malignant cells in a living organism and eliminate them in the same way," says Jean-Philppe Parvy, postdoctoral researcher at Cancer Research UK's Beatson Institute in Glasgow.

Their experiments showed that fruit flies prone to tumours produce more Defensin than their normal counterparts. Defensin interacts with dying tumor cells in animals. Closure of Defensin in tumor-prone animals leads to tumor growth, suggesting that Defensin actively kills cells while sparing normal cells.

Then, Parvy and his colleagues showed that Defensin recognizes tumor cells in the same way that he recognizes harmful microbes. The fly version of a protein called tumor necrosis factor helps to mark tumor cells for destruction and makes them more sensitive to Defensin attack. To do this, it brings a protein called phosphatidylserine to the surface of tumor cells. The defensin then binds to the phosphatidylserin-rich areas of the tumor cells and kills them.

"Our results reveal the anti-tumor role of defensin in flies and provide insight into the molecular mechanisms that make tumors sensitive to the action of MPAs," explains Parvy.

Further research is now needed to determine whether these same mechanisms are at work in mammals and humans.

"Our work could have significant potential for application to cancer research in mammalian models, as it raises the possibility that human MPAs may have anti-tumor effects similar to those of defensin in flies," explains Julia Cordero, principal investigator at the Institute of Cancer Sciences, University of Glasgow, UK. "If future work confirms it, natural MPAs or chemically engineered analogues could be used in cancer therapy."