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Cancer Res. 2014 Sep 15;74(18):5091-102. doi: 10.1158/0008-5472.CAN-13-3171.

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

Author information

1
Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
2
Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia.
3
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.
4
Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. Department of Biochemistry, The University of Melbourne, Parkville, Victoria, Australia.
5
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.
6
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.

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.

PMID:
25224959
DOI:
10.1158/0008-5472.CAN-13-3171
[Indexed for MEDLINE]
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