Berkeley Lab Scientists Find that Normal Breast Cells Help Kill Cancer Cells

It is well known that the human body has a highly developed immune system to detect and destroy invading pathogens and tumor cells. Now, researchers at the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) have shown that the body has a second line of defense against cancer – healthy cells. A new study shows that normal mammary epithelial cells, as they are developing, secrete interleukin 25, a protein known for its role in the immune system’s response to inflammation, for the express purpose of killing nearby breast cancer cells.

“We found that normal breast cells provide an innate defense mechanism against cancer by producing interleukin 25 (IL25) to actively and specifically kill breast cancer cells,” says breast cancer authority Mina Bissell, of Berkeley Lab’s Life Sciences Division, who led this research. “This suggests that IL25 receptor signaling may provide a new therapeutic target for the treatment of breast cancer.”

The results of this research are reported in the journal Science Translational Medicine in a paper titled “IL25 Causes Apoptosis of IL25R-expressing Breast Cancer Cells Without Toxicity to Nonmalignant Cells.” Co-authoring the paper with Bissell were Saori Furuta, Yung-Ming Jeng, Longen Zhou, Lan Huang, Irene Kuhn and Wen-Hwa Lee, of the University of California, Irvine, who along with Bissell is a corresponding author.

Although cancer remains a leading cause of premature death in the world today, most people live cancer-free lives for decades. In fact, the rate of cancer disease in the human population is surprisingly low given that the cells in our bodies are exposed on a daily basis throughout our lifetimes to radiation and chemical damage, plus a host of other factors that promote harmful DNA mutations and malignant tumors. It is not as if mutant cells are not being generated, explains Saori Furuta, lead author of the Science Translational Medicine paper and a Berkeley Lab colleague of Bissell’s.

“Even healthy individuals produce genetically impaired cells at the rate of up to 1,000 aberrant cells per day, however, as a part of homeostatic regulations, these cancer-prone cells are efficiently eradicated by the so- called tumor surveillance system of our body,” Furuta says. “A number of tumor surveillance mechanisms have been described in the past, including the classic molecular tumor suppressors, immune surveillance, and suppression by the extracellular matrix and other microenvironmental factors. We are now adding a new type of tumor suppression to this list, IL25 and other proteins secreted by normal breast cells that kill or subdue their mutated neighbors.”

This schematic shows the cytotoxicity of IL25 on breast cancer cells that express IL25 receptor (IL25R). Nonmalignant mammary epithelial cells (MECs) do not express IL25R and are resistant to apoptosis induced by IL25, whereas cancer cells that express IL25R are susceptible to IL25–induced apoptosis. (Image courtesy of Saori Furuta) In their study, Furuta, Bissell, Lee and their colleagues found that whereas IL25 was highly toxic to breast cancer cells, it did not harm normal breast cells. The selectivity, they discovered, is due to the presence of an abundance of exposed IL25 receptors on breast cancer cells. These IL25 receptors were absent on normal breast cells.