Advertisement

Breast Cancer Research and Treatment

, Volume 141, Issue 2, pp 317–324 | Cite as

Sulforaphane inhibits mammary adipogenesis by targeting adipose mesenchymal stem cells

  • Qinglin Li
  • Jixiang Xia
  • Yuan Yao
  • Da-wei Gong
  • Hongfei Shi
  • Qun Zhou
Brief Report

Abstract

It is now well accepted that tumor cells actively communicate with the tumor microenvironment (e.g., adipocytes) leading to the progression of breast cancer and other malignancies. It is also known that adipose mesenchymal stem cells (MSCs) have the ability to differentiate into mature adipocytes and initiate cytokine signaling within the tumor microenvironment. Here, we examine the role of MSC-differentiated adipocytes on breast cancer cell migration, and test the effects of sulforaphane (SFN, a dietary chemoprevention agent) on adipocyte–breast cancer cell interaction. Our results demonstrate that SFN promotes MSC self-renewal and inhibits adipogenic differentiation. Subsequently, SFN treatment of adipocytes considerably hinders cytokine communication with breast cancer cells, thereby decreasing breast cancer cell migration and tumor formation.

Keywords

Sulforaphane Mammary Adipogenesis Adipose Mesenchymal stem cells Breast cancer cells 

Notes

Acknowledgments

This work was supported by ACS (Q.Z.), NIH/NCI R01 (Q.Z.), and NIH (P30DK072488, D.W.G). The authors thank Carlo Mercado for help.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Galic S, Oakhill JS, Steinberg GR (2010) Adipose tissue as an endocrine organ. Mol Cell Endocrinol 316:129–139PubMedCrossRefGoogle Scholar
  2. 2.
    Cristancho AG, Lazar MA (2011) Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol 12:722–734PubMedCrossRefGoogle Scholar
  3. 3.
    Kolf CM, Cho E, Tuan RS (2009) Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation. Arthr res ther 9:204CrossRefGoogle Scholar
  4. 4.
    Sul HS (2009) Minireview: Pref-1: role in adipogenesis and mesenchymal cell fate. Mol Endocrinol 23:1717–1725PubMedCrossRefGoogle Scholar
  5. 5.
    Lefterova MI, Zhang Y, Steger DJ, Schupp M, Schug J, Cristancho A, Feng D, Zhuo D, Stoeckert CJ Jr, Liu XS et al (2008) PPARgamma and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale. Genes Dev 22:2941–2952PubMedCrossRefGoogle Scholar
  6. 6.
    Yeh WC, Cao Z, Classon M, McKnight SL (1995) Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins. Genes Dev 9:168–181PubMedCrossRefGoogle Scholar
  7. 7.
    Wang Y, Sul HS (2009) Pref-1 regulates mesenchymal cell commitment and differentiation through Sox9. Cell Metab 9:287–302PubMedCrossRefGoogle Scholar
  8. 8.
    Iyengar P, Combs TP, Shah SJ, Gouon-Evans V, Pollard JW, Albanese C, Flanagan L, Tenniswood MP, Guha C, Lisanti MP et al (2009) Adipocyte-secreted factors synergistically promote mammary tumorigenesis through induction of anti-apoptotic transcriptional programs and proto-oncogene stabilization. Oncogene 22:6408–6423CrossRefGoogle Scholar
  9. 9.
    Dirat B, Bochet L, Dabek M, Daviaud D, Dauvillier S, Majed B, Wang YY, Meulle A, Salles B, Le Gonidec S et al (2011) Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Res 71:2455–2465PubMedCrossRefGoogle Scholar
  10. 10.
    Heiss E, Herhaus C, Klimo K, Bartsch H, Gerhauser C (2001) Nuclear factor kappa B is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms. J Biol Chem 276:32008–32015PubMedCrossRefGoogle Scholar
  11. 11.
    Gamet-Payrastre L (2006) Signaling pathways and intracellular targets of sulforaphane mediating cell cycle arrest and apoptosis. Curr Cancer Drug Targets 6:135–145PubMedCrossRefGoogle Scholar
  12. 12.
    Lee JH, Moon MH, Jeong JK, Park YG, Lee YJ, Seol JW, Park SY (2012) Sulforaphane induced adipolysis via hormone sensitive lipase activation, regulated by AMPK signaling pathway. Biochem Biophys Res Commun 426:492–497PubMedCrossRefGoogle Scholar
  13. 13.
    Boquest AC, Shahdadfar A, Frønsdal K, Sigurjonsson O, Tunheim SH, Collas P, Brinchmann JE (2005) Isolation and transcription profiling of purified uncultured human stromal stem cells: alteration of gene expression after in vitro cell culture. Mol Biol Cell 16:1131–1141PubMedCrossRefGoogle Scholar
  14. 14.
    Li Q, Yao Y, Eades G, Liu Z, Zhang Y, Zhou Q (2013) Downregulation of miR-140 promotes cancer stem cell formation in basal-like early stage breast cancer. Oncogene. doi: 10.1038/onc.2013.226 Epub ahead of printGoogle Scholar
  15. 15.
    Castells M, Thibault B, Delord JP, Couderc B (2012) Implication of tumor microenvironment in chemoresistance: tumor-associated stromal cells protect tumor cells from cell death. Int J Mol Sci 13:9545–9571PubMedCrossRefGoogle Scholar
  16. 16.
    Bochet L, Meulle A, Imbert S, Salles B, Valet P, Muller C (2011) Cancer-associated adipocytes promotes breast tumor radioresistance. Biochem Biophys Res Commun 411:102–106PubMedCrossRefGoogle Scholar
  17. 17.
    Bechara C, Chai H, Lin PH, Yao Q, Chen C (2007) Growth related oncogene-alpha (GRO-alpha): roles in atherosclerosis, angiogenesis and other inflammatory conditions. Med sci monit: Int Med J Exp Clin Res 13:RA87–RA90Google Scholar
  18. 18.
    Zhu Q, Han X, Peng J, Qin H, Wang Y (2012) The role of CXC chemokines and their receptors in the progression and treatment of tumors. J Mol Histol 43:699–713PubMedCrossRefGoogle Scholar
  19. 19.
    Deshmane SL, Kremlev S, Amini S, Sawaya BE (2009) Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interf Cytokine Res 29:313–326CrossRefGoogle Scholar
  20. 20.
    Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S (2011) The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 1813:878–888PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Qinglin Li
    • 1
  • Jixiang Xia
    • 1
  • Yuan Yao
    • 1
  • Da-wei Gong
    • 2
  • Hongfei Shi
    • 3
  • Qun Zhou
    • 1
  1. 1.Department of Biochemistry and Molecular BiologyUniversity of Maryland School of MedicineBaltimoreUSA
  2. 2.Department of MedicineUniversity of Maryland School of MedicineBaltimoreUSA
  3. 3.Division of Nutrition ScienceNanjing University of Chinese MedicineNanjingChina

Personalised recommendations