期刊
CANCER RESEARCH
卷 74, 期 18, 页码 5091-5102出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-13-3171
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- National Health & Medical Research Council (NHMRC) of Australia [APP400037]
- Department of Defense Breast Cancer Research Program [BC045396]
- Cancer Council of Victoria, Australia [APP1006425, APP1009315]
- Komen for the Cure
- NHMRC
- National Breast Cancer Foundation of Australia
- National Breast Cancer Foundation [CG-10-04, PF-12-14] Funding Source: researchfish
The TGF beta 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 naive 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-kappa B (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. (C) 2014 AACR.
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