Excessive adiposity has long been associated with increased incidence of breast cancer in postmenopausal women, as well as with increased mortality of breast cancer, regardless of menopausal status. While adipose tissue-derived estrogen contributes to obesity-associated risk for estrogen receptor (ER)-positive breast cancer, the estrogen-independent impact of adipose tissue on tumor invasion and progression remains to be elucidated. Here we show that adipose stromal cells (ASCs) significantly stimulate migration and invasion of ER-negative breast cancer cells and tumor invasion in a co-transplant xenograft mouse model. Our study also identifies cofilin-1, a known regulator of actin dynamics, as a determinant for the tumor-promoting activity of ASCs. The cofilin-1-dependent pathway affects the production of interleukin 6 (IL-6) in ASCs. Depletion of IL-6 from ASC-conditioned medium abrogated the stimulatory effect of ASCs on the migration and invasion of breast tumor cells. Thus, our work uncovers a link between cytoskeleton-based pathway in ASCs and the stromal impact on breast cancer cells.
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