Interleukin 6 secreted from adipose stromal cells promotes migration and invasion of breast cancer cells

Oncogene. 2009 Jul 30;28(30):2745-55. doi: 10.1038/onc.2009.130. Epub 2009 Jun 1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adipocytes / physiology*
  • Animals
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cofilin 1 / physiology
  • Female
  • Humans
  • Interleukin-6 / metabolism
  • Interleukin-6 / physiology*
  • Male
  • Mice
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Stromal Cells / physiology
  • Transplantation, Heterologous
  • rho-Associated Kinases / physiology


  • Cofilin 1
  • Interleukin-6
  • ROCK1 protein, human
  • rho-Associated Kinases