Credit: Photo by L. Brian Stauffer

CHAMPAIGN, Ill. – Scientists working to understand the cellular processes that link high cholesterol to breast cancer recurrence and metastasis report that a byproduct of cholesterol metabolism causes some cells to send cancer-promoting signals to other cells send. These signals are packaged in membrane-bound compartments called extracellular vesicles.

Reported in the magazine endocrinology, the discovery could lead to the development of new cancer therapies, researchers say.

“Extracellular vesicles play an important role in normal physiology, but they have been involved in cancer biology before,” said study director Erik Nelson, professor of molecular and integrative physiology at the University of Illinois Urbana-Champaign. “These particles transport cargo from one cell to another. This cargo is important because it is diverse and acts as a communication network. But very little is known about what regulates the vesicles. “

In previous studies, Nelson and his colleagues found that 27-hydroxycholesterol, a byproduct of cholesterol metabolism, promotes tumor growth by attaching to estrogen receptors in various tissues, stimulating estrogen-responsive cancer cells to multiply and grow. The researchers also discovered that 27HC suppressed immune function.

To better understand how 27HC affects cells, the team exposed the metabolite to several cell types in the new study – including immune cells known as polymorphonuclear neutrophils.

“When we treated neutrophils, a type of white blood cell, with 27-hydroxycholesterol, they started spitting out extracellular vesicles,” said Nelson.

The vesicles contained a unique collection of signaling molecules, the researchers found. And when injected into mouse models of breast cancer, the vesicles “promoted both breast tumor growth and breast cancer metastasis,” Nelson said.

“This is an important study because it determines that a hormone or metabolite can regulate these extracellular vesicles,” said Nelson. “Understanding how this system works could prove useful therapeutically.”

Nelson is also Professor of Nutritional Science and a member of the Carl R. Woese Institute for Genomic Biology and the Cancer Center in Illinois.

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This work was supported by the National Cancer Center and the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health, along with the Alzheimer’s Association, the American Institute of Cancer Research, and the Department of Defense Breast Cancer Research Program.

Editor’s Notes:

To contact Erik Nelson, send an email [email protected]

The article “The Cholesterol Metabolite 27HC Increases Secretion of Extracellular Vesicles That Promote Breast Cancer Progression” is available online and from the U. of I. News Bureau.

Media contact
Diana Yates, Life Sciences Editor, U. of I. News Bureau
[email protected]

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