Interleukin 6 secreted from adipose stromal cells promotes migration and invasion of breast cancer cells.
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.
Walter
M
M
Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA.
Liang
S
S
Ghosh
S
S
Hornsby
P J
PJ
Li
R
R
D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D051338:Cofilin 1 / Q000502:physiology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D017154:Stromal Cells / Q000502:physiology; D014183:Transplantation, Heterologous; D054460:rho-Associated Kinases / Q000502:physiology
D051338:Cofilin 1; D015850:Interleukin-6; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases