High cholesterol levels have been associated with the spread of breast cancer to other parts of the body, but researchers do not yet know the cause of this correlation. Recently, a new study from the University of Illinois found that it is caused by a metabolic byproduct of cholesterol that acts on specific immune cells, which leads to the spread of cancer cells. The study, which has been published in Nature Communications, identifies a new potential drug target that inhibits the behavior of this dangerous cholesterol metabolite byproduct with a molecule called 27HC. Erik Nelson, professor of molecular and integrative physiology, who led the study, said, “About one in eight of women are afflicted with breast cancer. We have an initial treatment for this disease, but many women develop metastatic breast cancer, where the breast cancer cells spread to other parts of the body, and we don’t have an ideal treatment for that. We want to find out what drives the spread of breast cancer cells and whether we can use drugs to combat it.” Nelson’s research team fed mice with breast cancer using a high-cholesterol diet. The researchers determined that too much cholesterol promoted tumor growth and metastasis, while the mice treated with cholesterol-lowering statins had fewer metastatic cancer cells. They then went a step further and inhibited the enzyme that produces 27HC during cholesterol metabolism. Amy Baek, a postdoctoral fellow and first author of the paper, said, “By inhibiting the enzyme that produces 27HC, we found that metastasis of breast cancer cells was inhibited. This suggests that drug treatments targeting this enzyme are likely to be effective.” The researchers also found that specific immune cell (certain neutrophils and T cells) activity became abnormal at cancer cell metastasis sites with high levels of 27HC. Nelson said, “Normally, the body’s immune system is able to attack cancer cells, but we found that 27HC acts on immune cells, causing them to mistake cancer cells for good cells. So it holds the immune cells hostage and allows the cancer to spread.” Because 27HC works through the immune system and does not just target breast cancer itself, the researchers believe their findings have broad applicability to the treatment of solid tumors. They also conducted experiments targeting colon, lung, melanoma and pancreatic cancers and likewise found that 27HC enhanced the metastasis of cancer cells. This suggests that treatment targeting 27HC may be applicable to a wide range of cancers. Researchers are further defining the pathways by which 27HC acts on immune cells. Through a clinical collaboration with the Cali Foundation Hospital, the team is determining whether the same 27HC pathway exists in humans as it does in mice. We hope to develop small molecule drugs that inhibit 27HC,” Nelson said. Right now, there are good cholesterol-lowering drugs on the market: statins. Cancer patients who are at risk for high cholesterol can check with their own doctors.”