br The role of other bone
The role of other bone marrow cells in metastatic cancer growth Other cell types also that take part in the regulation of the bone microenvironment, including myeloid and immune cells (T cells), platelets, bone marrow endothelial and haematopoietic cells, as well as bone marrow-derived mesenchymal stem cells [3,162]. Some of these cells are likely to participate in the creation of the pre-metastatic niche [3,162]. Haematopoietic cells (other than osteoclasts) have the ability to potentially affect bone metabolism, and in particular bone resorption. For example, T cells produce osteoclast-activating factors such as RANKL, tumour necrosis factor (TNF) and TGF-β [91,163,164], It is via this link that these cells may influence cancer growth in bone. Furthermore, tumour cells are able to activate platelets to release lysophosphatidic acetylcholine receptors (LPA), which in turn promotes breast cancer growth and skeletal metastasis in mice via production of IL-6 and IL-8, again potentially augmenting the vicious cycle . In addition, myeloid-derived suppressor cells (MDSCs), platelets, bone marrow endothelial and haematopoietic cells as well as bone marrow-derived mesenchymal stem cells may all be involved in tumour neovascularisation . These cells may interact with other bone cells at various levels and participate in the process of bone metastasis [3,162]. While most of these events affect tumour growth by changing the bone microenvironment, some may have additional effects on cancer cell metastasis by co-operating with osteoblasts, osteocytes and osteoclasts in creating what is known as the pre-metastatic niche.
Acknowledgements This work has been supported in part by the following grants: Prostate Cancer Foundation of Australia (PCFA) (M.J.S, Y.Z, H.Z, C.R.D), University of Sydney Cancer Research Fund (M.J.S), National Health and Medical Research Council, Australia (NHMRC) (R.L.S, Program Grant 535903 and Fellowship 427601; C.R.D, M.J.S, and H.Z, Project Grant 352332; Y.Z, Early Career Fellowship 596870), Australian Cancer Research Foundation (R.L.S), RT Hall Trust (R.L.S), Petre Foundation (R.L.S).