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

M. Walter, S. Liang, S. Ghosh, P. J. Hornsby, R. Li

Research output: Contribution to journalArticle

179 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2745-2755
Number of pages11
JournalOncogene
Volume28
Issue number30
DOIs
StatePublished - Jul 30 2009

Keywords

  • Adipose stromal cells
  • Breast tumor cells
  • Cofilin-1
  • IL-6
  • Invasion
  • Migration

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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