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Oncogene. 2015 May 7;34(19):2437-49. doi: 10.1038/onc.2014.189. Epub 2014 Jul 7.

Inhibition of BMP signaling suppresses metastasis in mammary cancer.

Author information

1
Department of Cancer Biology and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
2
Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA.
3
1] Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University School of Medicine, Nashville, TN, USA [2] Department of Chemistry, Vanderbilt University College of Arts and Science, Nashville, TN, USA.
4
1] Research Medicine, Veterans Affairs TVHS, Nashville, TN, USA [2] Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
5
1] Department of Cancer Biology and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA [2] Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA.

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.

PMID:
24998846
PMCID:
PMC4689138
DOI:
10.1038/onc.2014.189
[Indexed for MEDLINE]
Free PMC Article
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