Study Suggests Mechanism Linking Diabetes and Breast Cancer

Researchers in California have suggested a mechanism behind breast cancer’s suppression of insulin production, which impairs blood sugar regulation and ultimately causes diabetes that, in turn, promotes tumor growth.

Breast cancer is the second most diagnosed malignancy, and more than 10% of the U.S. population has diabetes, with an estimated 2 in 5 Americans expected to develop the chronic disease during their lifetime.

Though they appear to be distinct diseases connected only by the fact they are both prevalent, past research has uncovered associations between the two. Women with diabetes have a 20­­­­-27% increased risk of developing breast cancer, and insulin resistance—a key characteristic of diabetes—has been associated with breast cancer incidence and poor survival.

Population studies also suggest diabetes risk begins to increase two years after a breast cancer diagnosis, and by 10 years post-diagnosis, the risk is 20% higher in breast cancer survivors than in age-matched women without breast cancer.

But these epidemiological linkages are not clear-cut or definitive, and some studies have found no associations at all. In a new paper, published recently in Nature Cell Biology, a research team led by scientists at University of California San Diego School of Medicine describes a possible biological mechanism connecting the two diseases.

In the study, they posit that breast cancer suppresses the production of insulin, resulting in diabetes, and the impairment of blood sugar control promotes tumor growth. “No disease is an island because no cell lives alone,” says corresponding study author Shizhen Emily Wang, PhD, professor of pathology at UC San Diego School of Medicine. “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.”

According to the study, the mechanism behind the connection involves extracellular vesicles (EV), spheres secreted or shed by cells that transport DNA, RNA, proteins, fats and other materials between cells. In this case, the cancer cells were found to be secreting microRNA-122 into the vesicles. Wang says when vesicles reach the pancreas, they can enter the islet cells responsible for insulin production, dispense their miR-122 cargo and damage the islets’ critical function in maintaining a normal blood glucose level.

“Cancer cells have a sweet tooth,” Wang adds. “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.”

The research was conducted using mouse models, which found that slow-releasing insulin pellets or a glucose-lowering drug known as an SGLT2 inhibitor restored normal control of glucose in the presence of a breast tumor, which in turn suppressed the tumor’s growth.

“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,” Wang said.