title: BMP4 inhibits breast cancer metastasis by blocking myeloid-derived suppressor cell activity.
abstract: The TGFβ growth factor family member BMP4 is a potent suppressor of breast cancer metastasis. In the mouse, the development of highly metastatic mammary tumors is associated with an accumulation of myeloid-derived suppressor cells (MDSC), the numbers of which are reduced by exogenous BMP4 expression. MDSCs are undetectable in naïve mice but can be induced by treatment with granulocyte colony-stimulating factor (G-CSF/Csf3) or by secretion of G-CSF from the tumor. Both tumor-induced and G-CSF-induced MDSCs effectively suppress T-cell activation and proliferation, leading to metastatic enhancement. BMP4 reduces the expression and secretion of G-CSF by inhibiting NF-κB (Nfkb1) activity in human and mouse tumor lines. Because MDSCs correlate with poor prognosis in patients with breast cancer, therapies based on activation of BMP4 signaling may offer a novel treatment strategy for breast cancer. Cancer Res; 74(18); 5091-102. ©2014 AACR.
authors.affiliation: Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Clare Y
authors.initials: CY
authors.lastname: Slaney
authors.affiliation: Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Bradley N
authors.initials: BN
authors.lastname: Bidwell
authors.affiliation: Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia.
authors.forename: Belinda S
authors.initials: BS
authors.lastname: Parker
authors.affiliation: Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. Department of Pharmacology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Cameron N
authors.initials: CN
authors.lastname: Johnstone
authors.affiliation: Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. Department of Biochemistry, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Jai
authors.initials: J
authors.lastname: Rautela
authors.affiliation: Morgan Welch Inflammatory Breast Cancer Research and Clinic, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. robin.anderson@petermac.org beckhardt@mdanderson.org.
authors.forename: Bedrich L
authors.initials: BL
authors.lastname: Eckhardt
authors.affiliation: Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia. robin.anderson@petermac.org beckhardt@mdanderson.org.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Anderson
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D022423:Myeloid Cells / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology; D009362:Neoplasm Metastasis; D015398:Signal Transduction
chemical_list: C525809:BMP4 protein, human; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D016328:NF-kappa B