Chapter 6 - Involvement of osteocytes in cancer bone niche

Abstract

Osteocytes are the most abundant cell type of the bone, representing 95% of all bone cells. Their basic functions are to maintain systemic mineral homeostasis and remodel bone mass according to environmental requirements, regulating both bone-forming osteoblasts and bone-resorbing osteoclasts, mainly through the receptor activator of nuclear factor kappa B (RANK)/RANK ligand (RANKL) biological pathway and sclerostin, a potent inhibitor of the canonical Wingless-type (Wnt) signaling. Bone metastases are common in patients with advanced cancer, with 65–75% of patients with breast or prostate cancer and over 35% of patients with lung cancer found to have bone metastases. Furthermore, multiple myeloma is characterized by the presence of osteolytic lesions in up to 80% of patients at diagnosis. The RANK/RANL/osteoprotegerin pathway and the canonical Wnt signaling play a key role in the development of solid tumor metastatic to the bone as well as in the biology of myeloma bone disease. Thus, osteocytes besides key regulators of bone homeostasis, participate in the bone tumor niche. From available data it is not clear how malignant cells interact with osteocytes in the bone microenvironment. Recent studies, however, have shown that these interactions lead to changes of the morphology, the genome and the viability of osteocytes and support a crucial role of osteocytes in the development of bone metastases and of myeloma bone disease. The aim of this review is to explore the possible role of osteocytes in malignant bone disease, according to all reported information in the current literature.