Production of interleukin-11 in bone-derived endothelial cells and its role in the formation of osteolytic bone metastasis

Abstract

The interactions of the cells in the bone microenvironment play important roles in bone remodeling. Osteoblasts are involved in the bone remodeling through the production of soluble factors that regulate proliferation and di erentiation of osteoclasts and through cell ± cell interactions. Histological studies have suggested that endothelial cells are also associated with some osteolytic bone diseases. However, it is still unclear how endothelial cells contribute to bone resorption. We established bone-derived endothelial cells (BDECs) to study their roles in bone remodeling. The established BDECs promoted bone resorption in a murine neonatal calvaria organ culture system by secreting a soluble bone resorption-inducing factor(s) when stimulated by several in¯ammatory cytokines. This bone resorptioninducing factor was identi®ed as interleukin-11 (IL-11). IL-11 is known to enhance bone resorption by promoting osteoclastogenesis and by suppressing the activity of osteoblasts. The production of IL-11 in BDECs was also promoted by conditioned medium of human melanoma A375M cells. Because A375M cells formed osteolytic bone metastasis in vivo, BDECs might be involved in pathological osteolysis by producing IL-11. These results suggest that endothelial cells in bone play important roles in the promotion of bone resorption by secreting IL-11 in physiological and pathological conditions.

Immunohistochemical study of receptor activator of nuclear factor kappa‐B ligand (RANK‐L) in human osteolytic bone tumors

“…PTHrP has also been shown to be produced by melanoma [13]. In addition, it has been shown that melanoma tumor cells may promote bone resorption by indirectly stimulating production of interleukin-11 and transforming growth factor-b from osteoblast like cells [14,15]. Hence, it may be the case that cytokines other than RANK-L are responsible for tumor-mediated bone destruction.…”

Internal radiotherapy of painful bone metastases

“…Primary tumor cells invade the surrounding tissue by producing proteolytic enzymes, thereby traversing the wall of small blood vessels and entering the circulation [8]. Although most tumor cells do not survive the protective host-surveillance mechanism in this initial stage [9,10], the surviving cells enter the bone marrow cavity [5] and are believed to adhere to the endothelium [11]. Tumor cells can then enter the bone and potentially form bone metastases, or the bone provides chemotactic factors to adhere the tumor cells [12,13].…”

CXCL13 is an arrest chemokine for B cells in high endothelial venules

“…The BC1 mouse endothelial cells were derived from the cortical bone of BALB/c mice 25 and used in detachment assays under flow as previously described. 7 A monolayer of BC1 cells was grown on a gelatin-coated plastic dish and placed in a flow chamber (Glycotech, Gaithersburg, MD).…”