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Ewing sarcoma (ES) is a primary malignant round cell tumour of bone characterized by rapid and extensive osteolysis. Cellular mechanisms underlying the rapid bone resorption in ES have not been characterized. Osteoclasts are marrow-derived multinucleated cells that effect tumour osteolysis. The role of ES tumour cells in influencing osteoclast formation and/or directly contributing to the osteolysis in ES has not been determined. Using a tissue culture bioassay, we found that lacunar resorption is not carried out by (CD99(+) ) ES tumour cells, but by (CD68(+) ) macrophage/osteoclast-like cells; this resorption occurred in the absence of the osteoclastogenic factor, receptor activator of nuclear factor κB ligand (RANKL). ES cell lines cultured directly on dentine slices did not resorb the mineral or organic components of the bone matrix. Immunohistochemistry of ES tissue microarrays, western blotting, and RT-PCR studies showed that ES cells strongly expressed both RANKL and macrophage-colony stimulating factor (M-CSF), two major osteoclastogenic factors. When co-cultured with human monocytes, ES cells induced the formation of TRAP(+) osteoclastic cells. Conditioned medium from cultured ES cells did not result in osteoclast formation, indicating that cell-cell contact is required for ES-induced osteoclastogenesis. Our findings indicate that ES cells do not resorb bone directly but that they may support osteoclast formation by a RANKL-dependent mechanism.

Original publication

DOI

10.1002/path.2869

Type

Journal article

Journal

The Journal of pathology

Publication Date

10/2011

Volume

225

Pages

195 - 202

Addresses

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Nuffield Orthopaedic Centre, University of Oxford, Windmill Road, Headington, Oxford, UK.

Keywords

Cells, Cultured, Osteoclasts, Humans, Bone Neoplasms, Osteolysis, Blotting, Western, Enzyme-Linked Immunosorbent Assay, Tissue Array Analysis, Immunohistochemistry, Reverse Transcriptase Polymerase Chain Reaction, Cell Differentiation, Adolescent, Adult, Infant, Female, Male, RANK Ligand, Sarcoma, Ewing