White blood cells help spread cancer, mouse study shows
Findings suggest existing drugs could prevent secondary tumours
White blood cells, key defenders in the body's immune system, can activate cancer cells and help them spread, a new study by Montreal and Calgary researchers suggests.
The findings likely explain why infection after surgery among cancer patients is associated with a higher death rate due to the spread of the cancer, the researchers reported in a paper published Monday in the Journal of Clinical Science.
'What's equally exciting is medications already exist that are being used for other non-cancer diseases, which may prevent this mechanism of cancer spread or metastasis.'—Lorenzo Ferri, RI-MUHC
"We are the first to identify this entirely new way that cancer spreads," said Lorenzo Ferri, a co-author of the paper, in a statement.
"What's equally exciting is medications already exist that are being used for other non-cancer diseases, which may prevent this mechanism of cancer spread or metastasis."
Ferri, director of the Division of Thoracic Surgery and the Upper Gastrointestinal Cancer Program at the Research Institute of the McGill University Health Centre, and his colleagues decided to examine the role of white blood cells more closely after noticing that cancer patients who had a severe infection after surgery were more likely to have their cancer return in the form of secondary tumours — tumours that later grow in parts of the body other than the site of the original tumour.
The researchers induced infections in mice by puncturing the cecum, a pouch located where the small and large intestine join. That caused their white blood cells to spring into action. The white blood cells produced web-like networks made of DNA called neutrophils extracellular traps (NETs). The NETs, which typically trap and kill pathogens such as bacteria, were clearly visible using a microscope in mice that had their cecum punctured, but not those who had a "sham" surgery that didn't cause infection.
Cancer cells were injected into both sets of mice. Afterward, the mice that had their cecum punctured had an average of 400 secondary tumours in their livers, compared to an average of two in the mice who had the "sham" surgery.
The researchers hypothesized that the NETs produced by the white blood cells trapped the cancer cells, and activated them instead of killing them. They managed to actually see this in experiments conducted on cells under a microscope.
When the mice with their cecums punctured were treated with drugs that prevent the formation of NETs, such as enzymes that break down DNA, they developed far fewer tumours — an average of 234 or 132, depending on the drug.
The researchers wrote that further studies are needed to validate their results, but the findings suggest it may be possible to reduce the spread of tumours among cancer patients who develop infections after surgery. They proposed that drugs targeting NET formation might be a potential new treatment for cancer patients.
The study was co-authored by Ferri's colleagues at McGill University and at the University of Calgary and was funded by the Canadian Cancer Society Research Institute.