Premium
Ewing sarcoma cells express RANKL and support osteoclastogenesis
Author(s) -
Taylor Richard,
Knowles Helen J,
Athanasou Nicholas A
Publication year - 2011
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2869
Subject(s) - rankl , osteoclast , osteolysis , multinucleate , bone resorption , chemistry , cd68 , macrophage colony stimulating factor , bone marrow , giant cell , cancer research , pathology , microbiology and biotechnology , macrophage , activator (genetics) , biology , receptor , immunohistochemistry , medicine , endocrinology , in vitro , biochemistry , surgery
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. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.