期刊
ONCOGENE
卷 28, 期 30, 页码 2745-2755出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2009.130
关键词
adipose stromal cells; cofilin-1; IL-6; breast tumor cells; migration; invasion
资金
- NCI [CA93506]
- DOD [W81XWH-06-1-034]
- NIA
- Owens Medical Research Foundation
- Glenn Foundation for Medical Research
Excessive adiposity has long been associated with increased incidence of breast cancer in post-menopausal women, and with increased mortality from breast cancer, regardless of the menopausal status. Although 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 needs to be elucidated. Here, we show that adipose stromal cells (ASCs) significantly stimulate migration and invasion of ER-negative breast cancer cells in vitro 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 of 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 the ASC-conditioned medium abrogated the stimulatory effect of ASCs on the migration and invasion of breast tumor cells. Thus, our study uncovers a link between a cytoskeleton-based pathway in ASCs and the stromal impact on breast cancer cells. Oncogene (2009) 28, 2745-2755; doi:10.1038/onc.2009.130; published online 1 June 2009
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