OREANDA-NEWS New research links natural and synthetic progestins and the production of specialized cancer cells that act like stem cells in the body.

“These cells greatly increase the likelihood of resistance to therapies and the risk for metastasis.”

The findings could help scientists target these rare cells that proliferate in breast cancers and metastasize elsewhere, and may help clinicians identify immunotherapies to combat the spread of the disease.

Hormone replacement therapies—medications containing female hormones that substitute those no longer produced by the body—are often prescribed to reduce the effects of menopausal symptoms in women. Previous research has indicated that women who take hormone replacement therapies have a higher incidence of breast cancer.

“In previous studies, we have shown that both natural and synthetic progestins accelerate the development of breast cancer and increase their metastasis to lymph nodes,” says Salman Hyder, a professor of biomedical sciences in the College of Veterinary Medicine and the Dalton Cardiovascular Research Center at the University of Missouri.

“Our laboratory is committed to identifying the cell mechanisms that bring about increased breast cancer risks. Recently, our research focused on special cells—which are called ‘cancer stem cell-like cells’—that induce aggressive tumor growth, metastasis, and cancer recurrence.”

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In a series of tests, the team used hormone-responsive human breast cancer cells to examine the effects of progestin on the cell markers typically found in breast cancers. Both natural and synthetic progestins significantly increased protein expression of CD44, a molecule involved in cell proliferation, cell communication, and migration.

Additionally, the presence of progestins caused these components to behave like cancer stem cell-like cells.

These rare cells are a small population of cells that—acting like normal stem cells—are self-renewing, create identical copies of themselves, and proliferate exponentially. Further testing showed that the rare subset of cancer cells actually was enriched by progestin.

“The findings show that exposure to natural and synthetic progestins leads to the development of these cancer stem-cell like cells,” Hyder says.

“These cells greatly increase the likelihood of resistance to therapies and the risk for metastasis. Our findings also suggest that clinicians may be able to combat the progestin-dependent tumor growth through immunotherapy.”

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The study appears in Breast Cancer—Targets and Therapy.

The College of Veterinary Medicine Committee on Research and the Ellis Fischel Cancer Center at the University of Missouri provided funding for the research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

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