Symmetric montage of immune tissue from fruit flies. Image credit: Jean-Philippe Parvy (CC BY 4.0)
Animals have a natural defence system – the immune system – that is needed to fight off disease-causing microbes, known as pathogens. One way the immune system attacks pathogens is by producing small microbe-killing molecules called antimicrobial peptides. These antimicrobial peptides carry a positive charge, which allows them to interact with and disrupt the negatively charged cell surfaces of many microbes. Healthy animal cells do not have these negatively charged components on their cell surface, which means they are invisible to antimicrobial peptides. Studies have reported that antimicrobial peptides can attack cancer cells grown in a dish. However, it was unclear whether they could fight cancer cells in a live animal.
Parvy et al. have now addressed this issue by studying tumours in the larvae of fruit flies. Flies with tumours made an antimicrobial peptide called Defensin, which normally helps to fight infections. When Parvy et al. deleted the gene coding for Defensin, less tumour cells were dying and the tumours became bigger. This result indicated that Defensin was protecting the fruit flies from tumours. Examining the tumours under the microscope showed that Defensin protein interacted with the membranes of tumour cells. Defensin was not, however, interacting with healthy cells.
Further analysis revealed that a negatively charged component of cell membranes called phosphatidylserine, which normally faces the inside of healthy cells, is exposed to the outer surface of tumour cells. This negatively charged molecule renders cancer cells visible to positively charged Defensin. Importantly, the exposure of the phosphatidylserine is mediated by the fly equivalent of a protein called Tumour Necrosis Factor, a key player in cancer biology. Defensin binding to tumour cells leads to their death.
These experiments in the fruit fly highlight key molecular mechanisms that allow antimicrobial peptides to fight cancer cells in a living organism. Because human tumour cells can also expose phosphatidylserine, these latest findings may open up the possibility of a new kind of anti-cancer therapy for patients.
