Antimicrobial peptides that help protect against infection defend against cancer

An antimicrobial agent called Defensin kills tumor cells and shrinks tumor 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 recognizing malignant cells in a living organism and eliminating them in a similar manner,"

Jean-Philppe Parvy, Study Lead Author and Postdoctoral Fellow, Cancer Research UK's Beatson Institute in Glasgow

Their experiments showed that tumor-prone fruit flies produce more Defensin than their normal counterparts. Defensin interacts with dying tumor cells in the animals. Shutting down Defensin in the tumor-prone animals leads to tumor growth, suggesting that Defensin is actively killing the cells while sparing normal cells.

Next, Parvy and his colleagues showed that Defensin recognizes tumor cells in the same way it recognizes harmful microbes. The fly version of a protein called Tumour Necrosis Factor helps flag the tumor 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 tumor cells. Defensin then binds to phosphatidylserine-rich areas on the tumor cells and kills them.

"Our results reveal an anti-tumor role for Defensin in flies and provides insights on the molecular mechanisms that make tumors 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-tumor effects similar to those of Defensin in flies. If future work confirms this, natural AMPs or chemically designed analogs might be used in anti-cancer therapeutics."

Julia Cordero, Study Senior Author and Senior Research Fellow, Institute of Cancer Sciences, University of Glasgow, UK

Source:
Journal reference:

Parvy, J. et al. (2019) The antimicrobial peptide defensin cooperates with tumour necrosis factor to drive tumour cell death in Drosophila. eLife. doi.org/10.7554/eLife.45061

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