Bone Abstracts

Advanced-stage prostate and breast cancer patients commonly develop bone metastases, accounting for significant clinical problems such as pain, fracture, immobility and death. Bone is comprised of diverse cell types that are potentially involved in metastatic progression. However, how cancer cells interact with these cells within the bone microenvironment to support their expansion and activity remains unclear. Recent data from our laboratory highlighted a novel feed-forward mechanism underlying the interactions between prostate cancer cells and a pro-tumorigenic subset of immature myeloid cells in the bone marrow. Briefly, levels of tumor derived parathyroid hormone-related protein (PTHrP) correlated with myeloid-derived suppressor cell (MDSC) recruitment in the tumor tissue, with further evidence for tumor-derived PTHrP potentiates MDSC activity and function within the bone marrow of tumor hosts. Mechanistic investigations in vivo revealed that PTHrP elevated Y418 phosphorylation levels in Src family kinases in MDSC via osteoblast-derived interleukin-6 and VEGF-A, thereby upregulating MMP-9. Taken together, our results showed that prostate cancer–derived PTHrP acts in the bone marrow to potentiate MDSCs, which are recruited to tumor tissue where they contribute to tumor angiogenesis and growth. Furthermore, we demonstrated that osteal macrophages mediate anabolic actions of parathyroid hormone. Collectively, this presentation will describe the distinct roles of myeloid-lineage bone marrow cells in bone during the progression of bone metastasis, and will discuss the potential therapeutic approaches.