Clinical & Experimental Metastasis

, Volume 29, Issue 4, pp 327–338 | Cite as

Augmented autocrine bone morphogenic protein (BMP) 7 signaling increases the metastatic potential of mouse breast cancer cells

  • Hirofumi Sakai
  • Mutsuo Furihata
  • Chie Matsuda
  • Munehisa Takahashi
  • Hiroshi Miyazaki
  • Takeo Konakahara
  • Toru Imamura
  • Tomoko Okada
Research Paper

Abstract

As malignant breast cancers progress, they acquire the ability to spread to other regions of the body, including bone and lung, but the molecular mechanism underlying the increase in metastatic potential is not fully understood. Here we studied murine 4T1E/M3 highly bone marrow metastatic breast cancer cells, which we established previously. These cells show upregulated expression of bone morphogenetic protein (BMP) 7 and BMP receptors, as well as augmented phosphorylation of Smad1/5/8. Both anchorage-independent cell growth measured in colony forming assays and cell migration measured in wound healing assays were suppressed in 4T1E/M3 cells following treatment with a neutralizing anti-BMP7 antibody or knockdown of BMP7 gene expression. In addition, metastasis of 4T1E/M3 cells to the spine and lung and intracellular levels of phosphorylated Smad1/5/8 were suppressed by knocking down BMP7. Conversely, overexpression of BMP7 in the weakly metastatic parental 4T1E cells augmented their anchorage-independent growth, migration and metastasis to spine and lung. Taken together, our results strongly suggest that augmented autocrine BMP7 signaling leads to increases in the anchorage-independent cell growth, migration and metastatic potential in our bone marrow metastatic breast cancer model.

Keywords

Breast caner Metastasis BMP7 Anchorage-independent growth Migration 

Notes

Acknowledgments

We thank Ms. Yoko Ezaki for her technical assistance. This work was supported in part by the Japan Science and Technology Agency (JST).

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Hirofumi Sakai
    • 1
    • 4
  • Mutsuo Furihata
    • 2
  • Chie Matsuda
    • 1
  • Munehisa Takahashi
    • 1
  • Hiroshi Miyazaki
    • 3
  • Takeo Konakahara
    • 4
  • Toru Imamura
    • 1
  • Tomoko Okada
    • 1
  1. 1.Signaling Molecules Group, Biomedical Research InstituteNational Institute of Advanced Industrial Science and Technology (AIST)TsukubaJapan
  2. 2.Department of PathologyKochi Medical SchoolNankokuJapan
  3. 3.Virginia Commonwealth University, Philips InstituteRichmondUSA
  4. 4.Faculty of Science and TechnologyTokyo University of ScienceNodaJapan

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