Bone, a Secondary Growth Site of Breast and Prostate Carcinomas: Role of Osteocytes

Abstract

Bone is the primarily preferred site for breast and prostate cancer to metastasize. Bone metastases are responsible for most deaths related to breast and prostate cancer. The bone's particular microenvironment makes it conducive for the growth of cancer cells. Studies on bone metastasis have focused on the interaction between cancer cells and the bone microenvironment. Osteocytes, the most common cell type of bone tissue, have received little attention in bone metastasis, although they are master signal sensors, integrators, and skeleton transducers. They play an important role in regulating bone mass by acting on both osteoblasts and osteoclasts, through the release of proteins such as sclerostin, Dickkopf-1 (DKK-1), and fibroblast growth factor 23 (FGF23). Osteocytes have been extensively re-evaluated, in light of their multiple functions: with different experimental approaches, it has been shown that, indeed, osteocytes are actively involved in the colonization of bone tissue by cancer cells. The present review focuses on recent research on the role that osteocytes play in bone metastasis of breast and prostate cancers. Moreover, the studies here summarized open up perspectives for new therapeutic approaches focused on modulating the activity of osteocytes to improve the condition of the bone metastatic patients. A better understanding of the complex interactions between cancer cells and bone-resident cells is indispensable for identifying potential therapeutic targets to stop tumor progression and prevent bone metastases.

Keywords: Dickkopf-1(DKK-1); bone metastasis; breast cancer; fibroblast growth factor 23 (FGF23); osteocytes; prostate cancer; sclerostin.

Figure 1

Overview of the effects of osteocyte products on osteoclasts and osteoblasts during bone metastasis. Also shown are the effects on osteoblasts and osteoclasts of sclerostin and DKK-1 produced by breast and prostate cancer cells at the metastatic site. DKK-1: Dickkopf-1; Wnt: Wingless-related integration site; RANKL: receptor activator of nuclear factor kappa B ligand; OPG: osteoprotegerin; FGF23: fibroblast growth factor 23; BPM: bone morphogenetic protein. (Figure created, with small modifications, using Servier Medical Art available at https://smart.servier.com).