Tumor Traps

After surgery to remove a tumor, neutrophils recruited to the site spit out sticky webs of DNA that aid cancer recurrence.

By | April 1, 2016

GOTCHA: After surgery, mouse neutrophils send out a tangle of DNA fibers (green; with arrows) called extracellular traps that facilitate the return of a cancer.ALLAN TSUNG

EDITOR'S CHOICE IN CELL AND MOLECULAR BIOLOGY

The paper
S. Tohme et al., “Neutrophil extracellular traps promote the development and progression of liver metastases after surgical stress,” Cancer Res, doi:10.1158/0008-5472.CAN-15-1591, 2016.

The cure and the cause
For colorectal cancers that have metastasized to the liver, surgeons are often called in to remove tumors. But in the majority of cases, the cancer comes back. Allan Tsung, a cancer surgeon at the University of Pittsburgh School of Medicine, suspected that the procedure itself—specifically, the body’s own healing response to surgical stress—might contribute to recurrence.

Cellular snares
Immune cells called neutrophils are first responders after injury caused by surgery. The cells are known to spew weblike DNA—a.k.a. neutrophil extracellular traps (NETs)—into the bloodstream. NETs were initially appreciated for capturing pathogenic bacteria, but are now emerging as important in cancer and other diseases. Tsung and his colleagues found that patients’ serum contained NETs after cancer surgery, and the greater the abundance of NETs, the higher the risk of recurrence. Treating mice with DNAse reduced NET levels and metastasis rates.

What’s going on
Cancer surgeon Lorenzo Ferri of McGill University who studies NETs says circulating cancer cells can be captured by NETs, which are decorated with numerous proteins that interact with tumor cells. “Cancer cells are actually activated by the NETs, increasing their ability to live and develop secondary tumours, or metastases,” he wrote in an email.

Do not disturb
Tsung says that for centuries people have advised against disturbing a tumor, lest it get worse. “A lot of people think it’s an old wives’ tale, but there may be some truth to it.” With surgery still the best option for metastatic colorectal cancer, however, Tsung would like to find a therapeutic that could rein in NETs while not interfering with neutrophils’ beneficial functions.

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