Bone Abstracts

A number of cancers develop in the skeleton or will metastasize to bone, including multiple myeloma and solid tumours such as breast and prostate cancer. Once established in the skeleton, cancer cells have the ability to modify the environment and cause devastating bone disease. The last decade has seen considerable progress in defining the critical cellular and molecular mechanisms responsible and also identified new roles for the cells of bone in the pathogenesis of metastasis process.

Tumour cells produce molecules, including parathyroid hormone-related protein, macrophage inhibitory protein 1α, and in some cases the ligand for receptor activator of NF_kB (RANKL), and induce RANKL in cells of the bone environment, to promote osteoclastic bone resorption. Tumour cells also produce molecules to either suppress bone formation, which is typically seen in osteolytic disease, or promote bone formation, which leads to osteosclerotic disease. Promoting bone formation and retaining the coupling between resorption and formation prevents osteolytic disease suggesting osteoblasts are in a pivotal position in determining the nature of the bone disease.

In addition, there is now increasing evidence that osteoblasts and osteoclasts play a critical role in supporting the growth and survival of cancer cells in the skeleton. Colonising cancer cells locate to dedicate niches in the skeleton and may compete with haemopoietic stem cells (HSC) for the HSC niche. Cells of the osteoblast lineage play a key role in the HSC niche and may support the immediate homing of cancer cells to the skeleton, their survival and long-term quiescence. Furthermore, switching on bone turnover increases the number of tumour lesions in the skeleton and inhibitors of resorption stop this process, arguing for a key role for the osteoclast in activating tumour cells. These data suggest that bone cells have unique relationship with tumour cells, supporting their colonization and activation as well as mediating the skeletal effects. Understanding these interactions, is likely to result new approaches to preventing tumour growth in the skeleton.