(Boston)—Obesity, insulin resistance and Type 2 diabetes are risk factors for breast cancer in post-menopausal women. The metabolic and inflammatory complications of obesity have a role in the formation of cancer. However, the cellular and molecular pathways that mediate breast cancer incidence, progression and metastasis in patients who also have metabolic complications are still not fully understood.
For the first time, researchers have found that exosomes (small vesicles secreted by many cell types and released into blood or nearby tissues and fluids), are involved in breast cancer progression and treatment resistance.
"We have identified a potential biological difference that might explain this higher risk and inform clinical decision making. This novel biology may also suggest new drugs or treatments to reduce risk for metastasis in cancer patients who are also obese and diabetic," explained corresponding author Gerald V. Denis, PhD, professor of medicine and pharmacology, and Shipley Professor, at Boston University School of Medicine.
Currently, more than 100 million Americans are currently diabetic or pre-diabetic with 90 percent of these cases due to obesity. If these adults develop an obesity-driven cancer, there is higher likelihood that the cancer will metastasize or become resistant to targeted treatments or hormone therapies.
The researchers isolated and characterized exosomes to identify factors that promote breast cancer progression and metastasis. They found that exosomes from insulin resistant adipocytes (fat cells), or from adipose tissue of adults with Type 2 diabetes, provoked much more dangerous changes in human breast cancer cells than exosomes from insulin sensitive or non-diabetic adipocytes.
According to Denis, metabolic diagnoses (blood glucose, A1c levels, lipid profiles, elevated insulin, cardiovascular risk markers like elevated CRP) are not normally considered by oncologists who are evaluating the risk of breast cancer progression, treatment resistance or recurrence. "It has also been difficult to identify blood tests that would assist clinicians to plan treatment or change treatment plans, because clinical trials have not yet been conducted to define the most important biomarkers. Inexpensive diagnostic and prognostic tests that are covered by insurance and that require only a small amount of blood would help oncologists improve treatment for these patients," he said.
Denis believes this discovery has implications for any obesity-related cancer (breast cancer in post-menopausal women, ovarian, uterine/endometrial, and (in men) prostate cancer, and (in both men and women) colorectal, gallbladder, renal, pancreatic, hepatic, thyroid, esophageal adenocarcinoma, and multiple myeloma) where nearby fat deposits may be metabolically abnormal and inflamed.
These findings appear online in the journal Science Signaling.
Funding was provided by the Cancer Systems Biology Consortium of the National Cancer Institute (GVD: U01CA182898, U01CA243004, R01CA222170) and the National Institute of Diabetes and Digestive and Kidney Diseases (SRF: R01DK117161; P30DK046200 to Adipose Biology and Nutrient Metabolism Core of Boston Nutrition and Obesity Research Center).
