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

Oncogene volume 28, pages 2745–2755 (2009)Cite this article

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.

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Acknowledgements

We thank Dr Adam Katz for ASCs. The work was supported by grants to RL from the NCI (CA93506) and DOD (W81XWH-06-1-034), and by grants to PJH from the NIA, the Owens Medical Research Foundation, and the Glenn Foundation for Medical Research.

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Authors and Affiliations

  1. Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    M Walter, S Ghosh & R Li

  2. Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    S Liang & P J Hornsby

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  1. M Walter
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Correspondence to R Li.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Walter, M., Liang, S., Ghosh, S. et al. Interleukin 6 secreted from adipose stromal cells promotes migration and invasion of breast cancer cells. Oncogene 28, 2745–2755 (2009). https://doi.org/10.1038/onc.2009.130

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