In Post-Menopausal Women Natural and Synthetic Progestin Therapies Help Breast Cancer Grow and Spread

Mizzou scientists discover hormone replacement treatments could cause specialized cancer cells to induce growth, metastasis. Hormone replacement treatments or medications containing female hormones that substitute those never again created by the body, regularly are recommended to reduce the effects of menopausal symptoms in women. Research has shown that women who take hormone replacement treatments have a higher incidence of breast cancer.

Currently, scientists at the University of Missouri have connected natural and synthetic progestins to the body’s production of specialized cancer cells that act like stem cells in humans. In breast cancers and metastasize somewhere else, discoveries could help researchers to focus on these rare cells that proliferate and may help clinicians to recognize immunotherapies to combat the spread of the disease.

Salman Hyder, the Zalk Endowed Professor in Tumor Angiogenesis and professor of biomedical sciences in the College of Veterinary Medicine and the Dalton Cardiovascular Research Center said, “In past studies, we have demonstrated that the development of breast cancer,  both natural and synthetic progestins accelerate and increase their metastasis to lymph nodes.

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

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

Moreover, the presence of progestins caused these components to behave like stem cell-like cells. These rare cells are a small population of cells that act like normal stem cells are self- renewing, make identical copies of them and exponentially proliferate. Further testing demonstrated that the rare subset of cancer cells really was enriched by progestin.

Hyder said, “The discoveries demonstrate that exposure to natural and synthetic progestins prompts the development of these cancer stem-cell like cells. These cells greatly improve the probability of protection from treatments and the risk for metastasis.

Our discoveries also recommend that clinicians might have the ability to combat the progestin- dependent tumor growth through immunotherapy.” Researchers involved with the study included Sandy Goyette, a graduate student in Hyder’s labYayun Liang, a research associate professor of biomedical sciences in the College of Veterinary Medicine and the Dalton Cardiovascular Research Center at MU; Benford Mafuvadze, formerly a post-doctoral fellow in Hyder’s lab; Matthew T. Cook, a current doctoral graduate and research researcher at Dalton Cardiovascular Research Center; and Moiz Munir, a Division of Biological Sciences and Capstone Scholar in Hyder’s lab.

The study, ” Natural and synthetic progestins advance cancer stem cell-like cells in hormone-responsive human breast cancer cell populations in vitro“, recently was published in Breast Cancer Targets and Therapy with funding provided on Research and the generosity of donors to the Ellis Fischel Cancer Center at MU through the College of Veterinary Medicine Committee. The content is exclusively the responsibility of the authors and does not necessarily represent the official views of the funding agencies.


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