BoneKEy Reports | BoneKEy Watch
IRF7 expression associated with low risk of bone metastasis
DOI:10.1038/bonekey.2012.191
A comparison of the transcriptomes of cells from primary tumors and metastatic tumors in an established mouse model of spontaneous metastasis has demonstrated that several genes suppressed during metastasis code for proteins targeted by Irf7, one of the main interferon (IFN) regulatory factors. Evidence from several lines of experimentation in mice showed that host immune cells received signals through the IFN pathway that enable Irf7 to suppress metastasis.
The researchers then switched their attention to the role of the IRF7 gene in patient samples; human primary tumors expressed IRF7, but expression was lost in samples from metastatic tumors, including those that had localized in bone. Only 16.7% of distant metastases expressed the gene compared with 56% (9/16; P<0.04) in the corresponding primary tumors.
Analysis of a publically available gene expression dataset of human primary tumors and with corresponding distant metastases also showed that expression of IRF7 was significantly associated with an extended survival period in which bone metastases did not arise. Reduced expression of IRF7, and the genes associated with it, was associated with a higher rate of bone metastases but not with metastasis to other sites such as liver, lung and brain.
Editor's comment: Bidwell and colleagues show for the first time that the Irf7 innate immune pathway is crucial for the suppression of breast cancer bone metastases. This study provides strong support for the use of interferon-based therapies in patients with advanced breast cancer.
This work is licensed under a
Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.