Researchers at the University of Fribourg have discovered a mechanism in the body that can have serious consequences for women with breast cancer. Granulocytes, a type of white blood cell that is active in cases of acute inflammation, make it easier for metastases to form. There is good news though. Ways exist to inhibit this potentially fatal process.

Breast cancer is the most common form of cancer among women. While early detection and current treatments offer most patients a very good chance of being cured, a quarter of the cases unfortunately metastasize, leading to a number of well-known consequences. This dangerous progression is caused by an inflammation occurring in and around the tumor. If treatment could modulate inflammation, it would open up new therapeutic possibilities. A way to do this effectively has yet to be found, however.

A hijacked defensive mechanism
The team led by Professor Curzio Rüegg of the University of Fribourg, working with Dr. Qiang Lan of the University of Helsinki and Dr. Sanam Peyvandi of the University of Lausanne, along with a number of additional researchers and the Swiss Institute of Bioinformatics of the Lausanne University Hospital (CHUV), has identified a new mechanism linking inflammation and metastasis. Granulocytes, a type of white blood cell that is commonly present during acute inflammation, facilitate the formation of metastases. “In a way, the cancerous cells push the granulocytes at the tumor site to produce inflammatory mediators, interleukin 6 and oncostatin,” Professor Rüegg explains. “It is these two mediators that subsequently transform breast cancer cells into cancer stem cells with a high metastatic capacity.” The researchers have shown that inhibiting the interleukin 6 and oncostatin produced by the granulocytes suppresses both the formation of cancer stem cells and metastases. Although the mechanism was discovered using laboratory models, the team demonstrated similar series of events in human breast cancer. To cap it all, the scientists also discovered a gene signature capable of identifying patients at increased risk of metastases because of the mechanism.

A major advance
To sum up, these results are original and important to both cancer research and clinical oncology for two reasons:

• The research reveals a new mechanism connecting granulocytes, cells that are normally present in cases of acute inflammation, with the appearance of more aggressive cancer cells that are responsible for metastasis formation.
• It identifies two inflammation factors that are the source of these effects, interleukin 6 and oncostatin, which could be targeted in therapy. Interleukin inhibitors are already available and effectively used to treat patients suffering from chronic inflammation.

This work opens up real opportunities for developing new therapies to treat patients who are at a high risk of metastases.