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A new study from the University of Illinois in the United States found that 27-hydroxycholesterol (27HC), a cholesterol metabolite, acts on specific immune cells, hijacking the immune system to promote cancer spread, or the "culprit" of cancer metastasis. The development of a small molecule drug that inhibits 27HC is expected to reduce the spread of tumor cells in cancer patients with high cholesterol.
Many people know that the accumulation of lipid cholesterol (cholesterol) in human arteries can lead to diseases such as myocardial infarction and stroke, but few people know about its other hazards.
Recently, researchers at the University of Illinois found that the cholesterol metabolite 27-hydroxycholesterol (27HC) acts on specific immune cells to help spread breast cancer to other parts of the body. The study was published in Nature Communications.
Inhibition of 27HC can reduce tumor metastasis
According to statistics: 1 out of every 8 women are breast cancer patients. Among them, many women will experience metastatic breast cancer after treatment, about 1 in 10 patients will metastasize within 5 years; if the cancer spreads to adjacent lymph nodes or tissues, the risk of metastasis will rise to 1/6. When breast cancer spreads to other tissues and organs, it is currently difficult to find effective treatments in medicine.
In this experiment, a team of professors, Erik Nelson, fed high-cholesterol foods to mice with breast cancer. It was found that high levels of cholesterol increased tumor growth and metastasis, while mice treated with the cholesterol-lowering drug statin had fewer metastases. As a result, they found through further research that statins inhibit the production of 27HC in cholesterol metabolism.
Professor Erik Nelson's team hopes to identify drivers of breast cancer metastasis and use relevant drugs for localization, such as the development of small molecule drugs to inhibit 27HC. In his view, for breast cancer patients with high cholesterol, try to use cholesterol-lowering statins for adjuvant therapy, or inhibit the spread of tumor cells.
27HC "fool" immune cells
"By inhibiting the production of 27HC enzymes, we found that the inhibitory factor has a metastatic effect on breast cancer. This indicates that 27HC is a biochemical medium that acts on γδT cells and neutrophils, and develops a drug that inhibits 27HC enzyme activity or An effective treatment," explains Amy Baek, a postdoctoral fellow at the University of Illinois.
"Under normal circumstances, the body's immune system can recognize and attack tumor cells," said Erik Nelson, professor of molecular and integrated physiology at the University of Illinois. "But we found that 27HC can act on immune cells, fooling them into treating tumor cells as healthy cells. Thus hijacking the immune system to promote the spread of cancer." In addition, they also found that specific immune cells (some types of neutrophils and γδ-T cells) abnormally move at the site of 27HC high metastasis; after 27HC inhibition, The number of cytotoxic CD8 + T lymphocytes decreased.
Can be applied to a variety of solid tumors
Since the cholesterol metabolite 27HC is "hijacking" the immune system rather than helping the breast cancer itself to metastasize, the researchers believe their findings have broad applicability to solid tumors.
As a result, they conducted experiments on colon cancer, lung cancer, melanoma and pancreatic cancer, and found that 27HC can increase the metastasis of all tumor types!
According to Professor Erik Nelson, this suggests that treatment with drugs targeting 27HC can be effective in a variety of cancer types, and we are expected to develop new drugs for the 27HC target.
In addition, the research team is actively exploring the pathways by which 27HC affects immune cells, and conduct clinical studies with partners to determine whether 27HC has the same mechanism of action in humans as in mice.
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