A recent study published in Nature Cell Biology from researchers at the University of California (UC) San Diego School of Medicine builds on earlier epidemiological studies already hinting at an associated risk of dysfunctional glucose metabolism in patients with breast cancer.
According to author Shizhen Emily Wang, PhD, professor of pathology at UC San Diego School of Medicine, although there is an associated risk of breast cancer and dysregulation of glucose metabolism, the mechanism by which this occurs remains unknown. Dr. Wang and the rest of the research team embarked on an effort to build upon previous work and epidemiological studies demonstrating that breast cancer alters glucose homeostasis and precipitates systemic dysregulation of glucose metabolism.
They tested the hypothesis in their study that identified extracellular vesicles (EV) were responsible, and it appeared that the cancer cells were secreting microRNA-122 into the vesicles. According to Dr. Wang, these vesicles enter the islet cells responsible for insulin production and suppress pancreatic insulin secretion, which results in blood glucose abnormality. Mice that were given high miR-122 EVs, or which had breast cancer tumors, exhibited impaired glucose tolerance and experienced fasting hyperglycemia.
Collaborating coauthors from UC San Diego included Minghui Cao, Roi Isaac, Wei Yan, Xianhui Ruan, Li Jiang, Yuhao Wan, Jessica Wang, Christine Caron, Donald P. Pizzo, Xuxiang Liu, Andrew R. Chin, Miranda Y. Fong, Oluwole Fadare, Richard B. Schwab, Wei Ying, and Jack D. Bui. Others were from affiliated facilities and universities.
"No disease is an island because no cell lives alone," stated Dr. Wang. "In this study, we describe how breast cancer cells impair the function of pancreatic islets to make them produce less insulin than needed, leading to higher blood glucose levels in breast cancer patients compared to females without cancer."
"Cancer cells have a sweet tooth," Dr. Wang added. "They use more glucose than healthy cells in order to fuel tumor growth, and this has been the basis for PET scans in cancer detection. By increasing blood glucose that can be easily used by cancer cells, breast tumors make their own favorite food and, meanwhile, deprive this essential nutrient from normal cells."
"These findings support a greater need for diabetes screening and prevention among breast cancer patients and survivors," stated Dr. Wang, noting that an inhibitor of miR-122, developed by Regulus Therapeutics, Inc. in San Diego is currently in clinical trial as a potential treatment for chronic hepatitis C. It has been found to be effective in restoring normal insulin production and suppressing tumor growth in mouse models of breast cancer.
Dr. Wang concluded, "These miR-122 inhibitors, which happen to be the first miRNA-based drugs to enter clinical trials, might have a new use in breast cancer therapy."
Earlier work by Dr. Wang examined how breast cancer also suppressed O-linked N-acetylglucosamine protein modification in muscle through the same extracellular-vesicle-encapsulated miR-122, which happens to also target a similar mechanism of cancer-associated muscle dysregulation as well.
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