BMP4 inhibits breast cancer metastasis by blocking myeloid-derived suppressor cell activity

• Published in: Cancer research (Chicago, Ill.) Ill.), 2014-09, Vol.74 (18), p.5091-5102
• Main Authors: Cao, Yuan, Slaney, Clare Y, Bidwell, Bradley N, Parker, Belinda S, Johnstone, Cameron N, Rautela, Jai, Eckhardt, Bedrich L, Anderson, Robin L
• Format: Article
• Language: English
• Subjects: Animals; Bone Morphogenetic Protein 4 - immunology; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Cell Line, Tumor; Female; Humans; Mammary Neoplasms, Experimental - immunology; Mammary Neoplasms, Experimental - pathology; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Nude; Myeloid Cells - immunology; Neoplasm Metastasis; NF-kappa B - immunology; Signal Transduction
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-13-3171

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.