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

Yuan Cao, Clare Y. Slaney, Bradley N. Bidwell, Belinda S. Parker, Cameron N. Johnstone, Jai Rautela, Bedrich L. Eckhardt, Robin L. Anderson

Research output: Contribution to journalArticleResearchpeer-review

62 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5091-5102
Number of pages12
JournalCancer Research
Volume74
Issue number18
DOIs
Publication statusPublished - Sep 2014
Externally publishedYes

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