There’s a mysterious relationship between diabetes and cancer that scientists are just beginning to understand, and new research may lead them to the answer.
But first, here’s why solving this mystery could be the proverbial game-changer for so many people:
- Breast cancer will affect one in eight women.
- Diabetes affects up to one-third of breast cancer patients.
- There are about 3.8 million women who have been diagnosed with breast cancer in the U.S.
Here’s the correlation: Obesity and type 2 diabetes increase the risk of breast cancer in post-menopausal women. These interrelated conditions and their complications can make the disease worse under a variety of circumstances and demographics.
What’s more, a researcher on the study tells Inverse the correlation to higher cancer risks among people with obesity and type 2 diabetes goes beyond breast cancer.
What’s new — Research published this week in the journal Science Signaling, reports on the discovery of evidence that communication pathways between cells may be involved in this little-understood correlation.
Researchers from Boston University discovered that type 2 diabetes may corrupt fat cells, causing them to load messenger vesicles called exosomes with a “payload” of metabolic information that triggers aggressiveness in breast cancer cells.
The discovery — The researchers took breast cancer cells and exposed them to breast fat cells from diabetic, cancer-free women. The diabetic fat cells released exosomes that delivered more cancer-linked proteins to the cancer cells, including the known gene corruptor TSP5.
“When you add them to the breast cancer cells, the genes that are turned on are all the bad guys,” Gerald V. Denis, co-author of the paper and co-director of the Boston University-Boston Medical Center Cancer Center, tells Inverse. “This is the signature of a really bad outcome.”
Also, there is no reason to think this effect is limited to breast cancer.
“This paper is about breast cancer,” Denis says. “But it’s true about any cancer.”
The effect shows the deep reach of diabetes into the body’s molecular level, he adds. “Diabetes is a chronic inflammatory disease and it screws up your immune system,” he says. “It’s like an infection that never ends.”
“We are not talking about a small number of people.”
The study notes that this finding does not indicate that obesity or diabetes cause cancer, but may help it spread and resist treatment.
Here’s the background — The role of these fat cells in cancer has not been well-understood, says Denis, even though scientists are increasingly knowledgeable about the stew of metabolic complications involved in diabetes and obesity and their possible effect on cancer.
“Population studies over 20 years have convincingly implicated cardiometabolic risk factors in incidence and progression of obesity-driven cancers, including breast cancers,” the paper reads.
“Numerous hormones, metabolites, cytokines, and tissue structural properties that change in concert with obesity, in both humans and animal models, have gained attention as potential mechanisms that link obesity and cancer. However, identification of the most important causal elements has been difficult.”
One possible reason for this dearth in understanding: Around the globe, type 2 diabetes and obesity are both more common to people of lower socioeconomic status. These people do not often form the basis of medical research.
“Part of the problem is that the standard of care [for breast cancer] is set by wealthy white patients at elite academic research universities,” says Denis These women have lower levels of obesity and type 2 diabetes than members of the average population.
Another reason is academic silos. Oncologists tend not to seek input from people outside the specialty, like biochemists looking at metabolic pathways. “There are separate fields that have not been talking to each other,” says Denis.
Why it’s important — “We are not talking about a small number of people,” says Denis. “There are 100 million people who are diabetic or pre-diabetic in the United States.”
What’s next — Denis hopes that this research informs insurance companies. Patients sometimes face difficulties getting complex glucose tests as part of cancer treatment. “None of the tests are covered by your insurance,” says Denis, “because it’s a different specialty.”
Abstract: Obesity and metabolic diseases, such as insulin resistance and type 2 diabetes (T2D), are associated with metastatic breast cancer in postmenopausal women. Here, we investigated the critical cellular and molecular factors behind this link. We found that primary human adipocytes shed extracellular vesicles, specifically exosomes, that induced the expression of genes associated with epithelial-to-mesenchymal transition (EMT) and cancer stem-like cell (CSC) traits in cocultured breast cancer cell lines. Transcription of these genes was further increased in cells exposed to exosomes shed from T2D patient–derived adipocytes or insulin-resistant adipocytes and required the epigenetic reader proteins BRD2 and BRD4 in recipient cells. The thrombospondin family protein TSP5, which is associated with cancer, was more abundant in exosomes from T2D or insulin-resistant adipocytes and partially contributed to EMT in recipient cells. Bioinformatic analysis of breast cancer patient tissue showed that greater coexpression of COMP (which encodes TSP5) and BRD2 or BRD3 correlated with poorer prognosis, specifically decreased distant metastasis–free survival. Our findings reveal a mechanism of exosome-mediated cross-talk between metabolically abnormal adipocytes and breast cancer cells that may promote tumor aggressiveness in patients with T2D.