BoneKEy Reports | BoneKEy Watch

Bone morphogenetic protein 7 suppresses distant tumor metastasis



DOI:10.1038/bonekey.2012.32

Finding new strategies to prevent recurrence of tumors at distant sites is a major priority in cancer research. A key focus is to elucidate the mechanisms by which metastatic tumor cells lay dormant in bone marrow after apparently successful treatment, only becoming active years later.

This study shows that bone stromal cells produce bone morphogenetic protein 7 (BMP7), which activates p38 mitogen-activated protein kinase. In turn, this boosts expression of p21, a cell cycle inhibitor, and N-myc downstream-regulated gene 1 (NDRG1), a metastasis suppressor gene, resulting in a sequence of molecular events that induces senescence in prostate cancer stem-like cells in mice.

The positive effects of BMP7 were dependent on expression of BMP receptor 2 (BMPR2), which matches well with observations that low BMPR2 expression in prostate cancer patients is associated with a higher incidence of bone metastasis. Interestingly, mice treated with BMP7 showed significantly suppressed growth of cancer stem cells in bone, and withdrawing BMP7 expression allowed tumor growth to recommence.

Editor's comment: The present study provides evidence that BMP7, which is secreted from bone marrow stromal cells, induces senescence of prostate cancer stem cells and suppresses skeletal tumor growth in animals. The findings warrant further research into the therapeutic potential of BMP7 in preventing metastatic bone disease in men with prostate cancer.


Creative Commons License This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.