Abstract
The skeleton is a unique structure capable of providing support for the body. Bone resorption and deposition are controlled in a tightly regulated balance between osteoblasts and osteoclasts with no net bone gain or loss. However, under conditions of disease, the balance between bone resorption and deposition is upset. Osteoblasts play an important role in bone homeostasis by depositing new bone osteoid into resorption pits. It is becoming increasingly evident that osteoblasts additionally play key roles in cancer cell dissemination to bone and subsequent metastasis. Our laboratory has evidence that when osteoblasts come into contact with disseminated breast cancer cells, the osteoblasts produce factors that initially reduce breast cancer cell proliferation, yet promote cancer cell survival in bone. Other laboratories have demonstrated that osteoblasts both directly and indirectly contribute to dormant cancer cell reactivation in bone. Moreover, we have demonstrated that osteoblasts undergo an inflammatory stress response in late stages of breast cancer, and produce inflammatory cytokines that are maintenance and survival factors for breast cancer cells and osteoclasts. Advances in understanding interactions between osteoblasts, osteoclasts, and bone metastatic cancer cells will aid in controlling and ultimately preventing cancer cell metastasis to bone.
Highlights
Bone is a unique organ of the body capable of providing structural support, regulation of calcium levels in blood, as well as protection of internal soft tissue organs [1]
Osteoblast conditioned media was a potent chemoattractant for metastatic breast cancer cells and elicited the formation of tartrate resistant acid phosphatase (TRAP)+ osteoclasts [50]. These results demonstrate that breast cancer cells utilize osteoblast-derived cytokines to facilitate breast cancer cell colonization and survival in the bone microenvironment. These results show that the osteoblast-derived cytokines IL-6, monocyte chemoattractant protein-1 (MCP-1), IL-8, GRO-alpha, and vascular endothelial growth factor (VEGF) are capable of stimulating osteoclastogenesis either in addition to or in the absence of the RANKL-RANK pathway [50]
These results suggest that alteration of osteoblast alignment in the bone matrix upon direct interaction with bone metastatic cancer cells may be mediated by gap junction signaling or cell-cell adhesion molecules
Summary
Bone is a unique organ of the body capable of providing structural support, regulation of calcium levels in blood, as well as protection of internal soft tissue organs [1]. To accomplish these functions, bone undergoes a dynamic process of remodeling to respond to mechanical strain and stress. Long bones, including the humerus and femur, as well as flat and irregular bones, such as vertebrae and the sternum, are predominantly composed of trabecular bone [5]. While both cortical and trabecular bone are metabolically active, trabecular bone undergoes remodeling at a rate higher than cortical bone [1]
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