Cholesterol Harnesses Immune Cells to Facilitate Breast Cancer Metastasis

The link between high cholesterol and breast cancer metastasis has been well-established; however, the underlying mechanisms of this relationship were previously unknown.

A study published by Nature Communications sheds light on how high cholesterol can accelerate the spread of cancer. The authors discovered that a byproduct of cholesterol metabolism—27HC—hijacks immune cells to fuel breast cancer metastasis.

Additionally, the authors discovered a potential treatment target that could inhibit 27HC’s actions.

“Breast cancer impacts roughly 1 in 8 women. We’ve developed fairly good strategies for the initial treatment of the disease, but many women will experience metastatic breast cancer, when the breast cancer has spread to other organs, and at that point we really don’t have effective therapies,” said lead researcher Erik Nelson, PhD. “We want to find what drives that process and whether we can target that with drugs.”

In the new study, mice models of breast cancer were fed a high cholesterol diet. The authors found that high cholesterol levels drove breast cancer growth and metastasis, but this effect was less pronounced in mice treated with statins, according to the study.

Next, the authors inhibited the enzyme that produces 27HC during cholesterol metabolism.

“By inhibiting the enzyme that makes 27HC, we found a suppressor effect on breast cancer metastasis,” said first author Amy Baek, PhD. “This suggests that a drug treatment targeting this enzyme could be an effective therapeutic.”

Notably, there was abnormal neutrophil and T cell activity at metastatic sites high in 27HC, according to the study.

“Normally, your body’s immune system has the capacity to attack cancer,” Dr Nelson said, “but we found that 27HC works on immune cells to fool them into thinking the cancer is fine. It’s hijacking the immune system to help the cancer spread.”

Since 27HC is thought to affect the immune system rather than breast cancer, the authors believe that their findings may be applicable to many solid tumors.

The investigators discovered that 27HC increased metastasis in colon cancer, lung cancer, melanoma, and pancreatic cancer, which suggests that inhibiting the cholesterol byproduct could prevent metastasis for these diseases, according to the study.

The authors said they are currently working to understand the pathway 27HC uses to affect the immune system and whether it uses the same pathway in humans.

“We hope to develop small-molecule drugs to inhibit 27HC,” Dr Nelson said. “In the meantime, there are good cholesterol-lowering drugs available on the market: statins. Cancer patients at risk for high cholesterol might want to talk to their doctors about it.”