BMP7 Induces Dormancy of Prostatic Tumor Stem Cell in Bone

Bone is the most common metastatic site for prostate cancer which affects approximately 70% of patients with advanced disease. Despite this clinical importance, the exact molecular mechanism of the bone-specific metastasis has not been clearly defined. The growth of the tumor cells in the bone is generally slow and they often become dormant until an appropriate microenviroment is established for their re-growth. According to the recent cancer stem cell theory, which still remains a hypotheses, recurrent tumor must arise from a dormant tumor stem cell. However, the precise mechanism of dormancy is virtually unknown, and identifying the responsible factors and understanding the underlining mechanism are crucial for developing a novel therapeutic approach. Our recent preliminary data suggest that BMP7 (bone morphogenetic protein 7) which is secreted from bone stromal cells is able to induce senescence to prostate tumor cells and that this induction is mediated by activation of the tumor metastasis suppressor gene, NDRG1 (N-myc downstream regulated gene 1). Therefore, we hypothesize that a prostatic tumor stem cell becomes dormant in the bone through the BMP7-mediated activation of p38 and NDRG1.
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