title: Prostate cancer promotes CD11b positive cells to differentiate into osteoclasts.
abstract: Bone is the preferred site of prostate cancer metastasis, contributing to the morbidity and mortality of this disease. A key step in the successful establishment of prostate cancer bone metastases is activation of osteoclasts with subsequent bone resorption causing the release of several growth factors from the bone matrix. CD11b+ cells in bone marrow are enriched for osteoclast precursors. Conditioned media from prostate cancer PC-3 cells induces CD11b+ cells from human peripheral blood to differentiate into functional osteoclasts with subsequent bone resorption. Analysis of PC-3 conditioned media revealed high amounts of IL-6 and IL-8. CD11b+ cells were cultured with M-CSF and RANKL, IL-6, IL-8, and CCL2, alone or in combination. All of these conditions induced osteoclast fusion, but cells cultured with M-CSF, IL-6, IL-8, and CCL2 were capable of limited bone resorption. Co-incubation with IL-6 and IL-8 and the RANK inhibitor, RANK-Fc, failed to inhibit osteoclast fusion and bone resorption, suggesting a potential RANKL-independent mechanism of functional osteoclast formation. This study demonstrates that functional osteoclasts can be derived from CD11b+ cells derived from human PBMCs. Prostate cancer cells secrete factors, including IL-6 and IL-8, that play an important role in osteoclast fusion by a RANKL-independent mechanism.
authors.affiliation: Departments of Internal Medicine and Urology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109-5946, USA.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Mizutani
authors.forename: Sudha
authors.initials: S
authors.lastname: Sud
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Pienta
mesh_terms: D001862:Bone Resorption; D039481:CD11b Antigen; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism / Q000502:physiology*; D016209:Interleukin-8 / Q000378:metabolism / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008297:Male; D010010:Osteoclasts / Q000473:pathology*; D019899:Paracrine Communication; D011471:Prostatic Neoplasms / Q000473:pathology*; D053245:RANK Ligand / Q000502:physiology*
chemical_list: D039481:CD11b Antigen; D017077:Culture Media, Conditioned; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D053245:RANK Ligand