Abstract
ABSTRACTAdvances in the last decade have established the osteocyte, the most abundant cell in bone, as a dynamic and multifunctional cell capable of controlling bone homeostasis by regulating the function of both osteoblasts and osteoclasts. In addition, accumulating evidence demonstrates that osteocyte function is altered in several skeletal disorders, and targeting osteocytes and their derived factors improves skeletal health. Despite the remarkable progress in our understanding of osteocyte biology, there has been a paucity of information regarding the role of osteocytes in the progression of cancer in bone. Exciting, recent discoveries suggest that tumor cells communicate with osteocytes to generate a microenvironment that supports the growth and survival of cancer cells and stimulates bone destruction. This review features these novel findings and discussions regarding the impact of chemotherapy on osteocyte function and the potential of targeting osteocytes for the treatment of cancer in bone. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Highlights
The skeleton is a multifunctional tissue that provides support and protection to various organs of the body, regulates mineral homeostasis and hematopoiesis, enables body movement, and has multiple endocrine functions in the body
In vitro studies show that mechanically stimulated osteocytes reduced the transendothelial migration of breast cancer cells.[68]. Further, interactions between osteocytes and endothelial cells decrease the expression of matrix metalloproteinase 9 (MMP-9), an enzyme known to facilitate the movement of metastatic cancer cells through the extracellular matrix.[68]. The disparity between these findings suggest that interactions between osteocytes and tumor cells are context and cancer specific
Cell-to-cell communication between myeloma cells and osteocytes activate Notch signaling in osteocytes, triggering caspase-3 mediated apoptosis.[79]. In addition, TNFa secreted by myeloma cells sustains/ amplifies osteocyte apoptosis.[79]. Giuliani and colleagues showed that myeloma cells stimulate osteocyte apoptosis by inducing autophagy.[92]. Consistent with the notion that apoptotic osteocytes attract osteoclast precursors to initiate targeted local bone resorption, conditioned media from osteocytes exposed to myeloma cells stimulates the recruitment of osteoclast precursors, and this effect was fully prevented by an inhibitor of osteocyte apoptosis.[79]. Together, these results identify apoptotic osteocytes as important contributors to the exaggerated bone resorption that drives the development of cancer-induced osteolytic lesions
Summary
The skeleton is a multifunctional tissue that provides support and protection to various organs of the body, regulates mineral homeostasis and hematopoiesis, enables body movement, and has multiple endocrine functions in the body.
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