Scientists from the Montreal-based Research Institute of the McGill University Health Center (RI-MUHC) report that, surprisingly, neutrophils appear to play a role in activating cancer cells in the body. And what would also seem to be counterintuitive is that these infection-fighting cells, which evolved to be the body’s first line of defense against pathogenic invaders, look like they make it easier for cancer cells to spread and form secondary tumors. This research, published today in the Journal of Clinical Investigation, has major implications for both the diagnosis and treatment of cancer.
"Our study reflects a major change in how we think about cancer progression," said Lorenzo Ferri, M.D., MUHC director of the division of thoracic surgery and the upper gastrointestinal cancer program. “And, more importantly, how we can treat it.”
According to Dr. Ferri, his team is the first to identify this new method of metastasis. The good news, he added, is that medicines already exist that are targeted at other noncancer diseases, and that these may prevent this particular form of metastasis. His group will now move to validate if these medications will work for the prevention and treatment of cancer metastasis and then determine the optimal timing and dosing.
Dr. Ferri and his colleagues came to their conclusions after conducting in vitro research and on a murine model of infection. They studied the formation of neutrophil extracellular traps (NETs), which are extracellular neutrophil-derived webs of DNA. These webs appear when inflammatory pathogens invade the body. According to Dr. Ferri, there was no known previous association between NETS and cancer progression.
“We report that circulating tumor cells become trapped within NETs in vitro under static and dynamic conditions,” he wrote in the Journal of Clinical Investigation paper. “In a murine model of infection using cecal ligation and puncture, we demonstrated microvascular NET deposition and consequent trapping of circulating lung carcinoma cells within DNA webs.
“NET trapping was associated with increased formation of hepatic micrometastases at 48 hours and gross metastatic disease burden at two weeks following tumor cell injection.”
Dr. Ferri pointed out that the team’s work implicates “NETs in the process of cancer metastasis in the context of systemic infection and [identifies] NETs as potential therapeutic targets.”
As a next step, his group showed that breaking down the neutrophil web is achievable by using certain medications, i.e., DNAse or neutrophil elastase inhibitor. Furthermore, in mice with cancer, markedly less tumor growth and metastasis occurred after the medication was administered.
This finding was true for a number of different cancer types, suggesting that neutrophil webs may be a common pathway involved in the spreading of many cancers.