Clinical & Experimental Metastasis

, Volume 29, Issue 4, pp 327–338

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

Authors

  • Hirofumi Sakai
    • Signaling Molecules Group, Biomedical Research InstituteNational Institute of Advanced Industrial Science and Technology (AIST)
    • Faculty of Science and TechnologyTokyo University of Science
  • Mutsuo Furihata
    • Department of PathologyKochi Medical School
  • Chie Matsuda
    • Signaling Molecules Group, Biomedical Research InstituteNational Institute of Advanced Industrial Science and Technology (AIST)
  • Munehisa Takahashi
    • Signaling Molecules Group, Biomedical Research InstituteNational Institute of Advanced Industrial Science and Technology (AIST)
  • Hiroshi Miyazaki
    • Virginia Commonwealth University, Philips Institute
  • Takeo Konakahara
    • Faculty of Science and TechnologyTokyo University of Science
  • Toru Imamura
    • Signaling Molecules Group, Biomedical Research InstituteNational Institute of Advanced Industrial Science and Technology (AIST)
    • Signaling Molecules Group, Biomedical Research InstituteNational Institute of Advanced Industrial Science and Technology (AIST)
Research Paper

DOI: 10.1007/s10585-012-9453-9

Cite this article as:
Sakai, H., Furihata, M., Matsuda, C. et al. Clin Exp Metastasis (2012) 29: 327. doi:10.1007/s10585-012-9453-9

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 canerMetastasisBMP7Anchorage-independent growthMigration

Copyright information

© Springer Science+Business Media B.V. 2012