DNA “webs” shown to promote metastasis in ovarian cancer

By Sally Robertson, B.Sc.Dec 19 2018Reviewed by Kate Anderton, B.Sc. (Editor)

Researchers at the University of Texas have found that DNA “webs” cast by immune cells aid the spread of ovarian cancer cells to new tissues (a process known as metastasis).

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The team also found that stopping immune cells from forming these webs reduced the extent of metastasis in an animal model, suggesting that a similar approach could be applied to prevent spread of the disease in humans.

Ovarian cancer is the fifth most common cause of death from cancer in women. During advanced stages of the disease, the cancer often spreads to a fatty tissue called the omentum.

The omentum is a large fold of serous membrane hanging down from the stomach that is sometimes referred to as the “policeman of the abdomen” because it houses immune cells that protect against infection in the abdomen.

Researchers are not yet clear about how and why ovarian cancer cells tend to spread to this tissue. Now, Dr. Honami Naora and her team have shown that, during the early stages of ovarian cancer, neutrophils take up residence in the omentum and start to extrude sticky webs of DNA referred to as ‘neutrophil extracellular traps’ (NETs).

Usually, the role of these webs would be to capture invading pathogens, but Naora and team have now demonstrated that the webs also capture circulating ovarian cancer cells, enabling them to proliferate in the omentum.

The study showed that these cancer cells secrete proinflammatory molecules that induce the accumulation of neutrophils in the omentum, which then extrude their NETs.

Ovarian cancer cells (red) can become trapped in sticky webs of DNA (green) released by immune cells known as neutrophils. (Credit: Lee et al., 2018)

In a mouse model, the researchers found that when they inhibited a key enzyme involved in this NET extrusion, the cancer cells were less able to spread to the omentum.

Currently, a common treatment approach to early-stage ovarian cancer is surgical removal of the omentum to prevent metastasis.

However, the team says their study suggests that stopping the ability of neutrophils to form these NETs could prevent the cancer from spreading, whilst still maintaining the protective function of the omentum.

Our study demonstrates that inhibiting NET formation decreases omental metastasis. Further studies of this intriguing host defense mechanism could yield new insights into improving ovarian cancer treatment.”

Dr. Honami Naora, Lead Researcher

The study, entitled “Neutrophils facilitate ovarian cancer premetastatic niche formation in the omentum”, was published in the Journal of Experimental Medicine on the 19^th December 2018.

Source

DNA 'webs' aid ovarian cancer metastasis, study reveals.