Inhibition of BMP signaling suppresses metastasis in mammary cancer

P. Owens, M. W. Pickup, S. V. Novitskiy, J. M. Giltnane, A. E. Gorska, C. R. Hopkins, C. C. Hong, H. L. Moses

Research output: Contribution to journalArticle

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Abstract

Bone morphogenetic proteins (BMPs) are secreted cytokines/growth factors that have differing roles in cancer. BMPs are overexpressed in human breast cancers, but loss of BMP signaling in mammary carcinomas can accelerate metastasis. We show that human breast cancers display active BMP signaling, which is rarely downregulated or homozygously deleted. We hypothesized that systemic inhibition of BMP signaling in both the tumor and the surrounding microenvironment could prevent tumor progression and metastasis. To test this hypothesis, we used DMH1, a BMP antagonist, in MMTV.PyVmT expressing mice. Treatment with DMH1 reduced lung metastasis and the tumors were less proliferative and more apoptotic. In the surrounding tumor microenvironment, treatment with DMH1 altered fibroblasts, lymphatic vessels and macrophages to be less tumor promoting. These results indicate that inhibition of BMP signaling may successfully target both the tumor and the surrounding microenvironment to reduce tumor burden and metastasis.

Original languageEnglish (US)
Pages (from-to)2437-2449
Number of pages13
JournalOncogene
Volume34
Issue number19
DOIs
StatePublished - May 7 2015

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Bone Morphogenetic Proteins
Breast Neoplasms
Neoplasm Metastasis
Tumor Microenvironment
Neoplasms
Bone Neoplasms
Lymphatic Vessels
Tumor Burden
Intercellular Signaling Peptides and Proteins
Down-Regulation
Fibroblasts
Macrophages
Cytokines
Lung

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Owens, P., Pickup, M. W., Novitskiy, S. V., Giltnane, J. M., Gorska, A. E., Hopkins, C. R., ... Moses, H. L. (2015). Inhibition of BMP signaling suppresses metastasis in mammary cancer. Oncogene, 34(19), 2437-2449. https://doi.org/10.1038/onc.2014.189

Inhibition of BMP signaling suppresses metastasis in mammary cancer. / Owens, P.; Pickup, M. W.; Novitskiy, S. V.; Giltnane, J. M.; Gorska, A. E.; Hopkins, C. R.; Hong, C. C.; Moses, H. L.

In: Oncogene, Vol. 34, No. 19, 07.05.2015, p. 2437-2449.

Research output: Contribution to journalArticle

Owens, P, Pickup, MW, Novitskiy, SV, Giltnane, JM, Gorska, AE, Hopkins, CR, Hong, CC & Moses, HL 2015, 'Inhibition of BMP signaling suppresses metastasis in mammary cancer', Oncogene, vol. 34, no. 19, pp. 2437-2449. https://doi.org/10.1038/onc.2014.189
Owens P, Pickup MW, Novitskiy SV, Giltnane JM, Gorska AE, Hopkins CR et al. Inhibition of BMP signaling suppresses metastasis in mammary cancer. Oncogene. 2015 May 7;34(19):2437-2449. https://doi.org/10.1038/onc.2014.189
Owens, P. ; Pickup, M. W. ; Novitskiy, S. V. ; Giltnane, J. M. ; Gorska, A. E. ; Hopkins, C. R. ; Hong, C. C. ; Moses, H. L. / Inhibition of BMP signaling suppresses metastasis in mammary cancer. In: Oncogene. 2015 ; Vol. 34, No. 19. pp. 2437-2449.
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