BMP7 Induces Dormancy of Prostatic Tumor Stem Cell in Bone.

摘要

Bone is the most common metastatic site for prostate cancer. 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. The recent stem cell theory predicts that the metastatic cells are a small population of stem-like cells in the primary tumor. However, the precise mechanism of dormancy is virtually unknown, and identifying the responsible factors and understanding their underlining mechanism are crucial for developing a novel therapeutic approach. Our preliminary data indicate that (i) bone morphogenetic protein 7 (BMP7) which is secreted from bone marrow stromal cells is able to induce senescence to prostate tumor cell and (ii) this induction is mediated by activation of the tumor metastasis suppressor gene, N-myc downstream regulated gene 1 (NDRG1). These results strongly suggest that the BMP7-NDRG1axis plays a critical role in dormancy of prostate tumor cells in the bone. The overall goal of this proposal is to elucidate the mechanism of BMP7-induced dormancy in tumor stem cells and explore a possibility of using BMP7 as an anti-metastatic drug for prostate cancer.