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Exosomes associated with breast cancer in patients with obesity

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. These findings, 'Adipocyte-derived exosomes may promote breast cancer progression in type 2 diabetes', appear online in the journal Science Signaling.

Three-dimensional culture of human breast cancer cells, with DNA stained blue and a protein in the cell surface membrane stained green m(Image created in 2014 by Drs Tom Misteli and Karen Meaburn at the NIH IRP)

"We have identified a potential biological difference that might explain this higher risk and inform clinical decision making,” explained corresponding author, Dr Gerald V. Denis, Ph.D., professor of medicine and pharmacology, and Shipley Professor, at Boston University School of Medicine. “This novel biology may also suggest new drugs or treatments to reduce risk for metastasis in cancer patients who are also obese and diabetic.”

The researchers isolated and characterised 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, oesophageal adenocarcinoma, and multiple myeloma) where nearby fat deposits may be metabolically abnormal and inflamed.


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