Obesity and metabolic diseases are strong risk factors for the development and progression of metastatic breast cancers in women who have completed menopause. Breast tumors contain a large number of white blood cells and adipocytes (i.e., fat cells); however, the role of adipocytes in metastatic breast cancer is unknown. Findings of a new report show that adipocytes shed molecular droplets called exosomes that relay cancer-promoting signals.
Adipocytes play a critical role in the tumor microenvironment, releasing proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-alpha and fats that act as fuel for tumor growth. Tumor metastasis is induced by changes in gene expression that increase cell movement and angiogenesis (i.e., the growth of new blood vessels) and decrease cell death and adhesion (i.e., how tightly cells cling to each other). The mechanisms by which adipocytes deliver these pro-cancer and pro-metastatic signals is understudied.
The investigators obtained estrogen receptor-positive breast cancer cells and co-cultured them with adipocytes that were collected from female patients with or without type 2 diabetes who underwent bariatric (weight-loss) surgery. The researchers measured changes in gene and protein expression and performed fluorescence imaging to observe physical changes to adipocytes and cancer cells.
When cultured with adipocytes from patients with obesity, cancer cells increased expression of genes important for a process called epithelial-to-mesenchymal transition, a key stage of tumor metastasis. Compared to exosomes produced by adipocytes from participants without type 2 diabetes, exosomes from participants with diabetes increased the expression of metastasis genes in cancer cells to a greater extent. Microscope imaging revealed that cancer cells from participants with diabetes underwent physical changes associated with metastasis as well as gene expression.
These results revealed that exosomes shed from adipocytes act as the mechanism for delivery of pro-cancer compounds from adipocytes to breast cancer cells. Also, the strength of this pro-cancer signaling increased as insulin resistance increased. This study provides important insight into the relationship between obesity and cancer.
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