title: Inhibition of BMP signaling suppresses metastasis in mammary cancer.
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.
authors.affiliation: Department of Cancer Biology and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: P
authors.initials: P
authors.lastname: Owens
authors.affiliation: Department of Cancer Biology and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Pickup
authors.affiliation: Department of Cancer Biology and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: S V
authors.initials: SV
authors.lastname: Novitskiy
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Giltnane
authors.affiliation: Department of Cancer Biology and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Gorska
authors.affiliation: 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.
authors.forename: C R
authors.initials: CR
authors.lastname: Hopkins
authors.affiliation: 1] Research Medicine, Veterans Affairs TVHS, Nashville, TN, USA [2] Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Hong
authors.affiliation: 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.
authors.forename: H L
authors.initials: HL
authors.lastname: Moses
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000517:prevention & control* / Q000556:secondary; D042601:Lymphatic Vessels / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011720:Pyrazoles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D019485:Bone Morphogenetic Proteins; C583032:DMH1 compound; D011720:Pyrazoles; D011804:Quinolines