RANK (receptor activator of nuclear factor kappa B) and RANK ligand are expressed in giant cell tumors of bone.
In giant cell tumors of bone (GCTBs), the mesenchymal stromal cells are the neoplastic cells and induce recruitment and formation of osteoclasts (OCs). Studies on recently discovered members of the tumor necrosis factor receptor-ligand family have demonstrated a crucial role of RANKL (receptor activator of nuclear factor kappa B [RANK] ligand) expressed by osteoblast/stromal cells and of its receptor RANK expressed by OCs during OC differentiation and activation. OCs typically are present in large numbers in GCTBs, suggesting that these tumors may contain cells expressing factors that stimulate OC precursor recruitment and differentiation. We used immunohistochemical analysis to study RANKL and RANK expression in 5 GCTBs. Multinucleated cells and some mononuclear cells showed strong positive staining with anti-RANK antibodies; RANKL was present in a subset of mononuclear cells that did not express the hematopoietic lineage cell marker CD45, a feature that identified them as mesenchymal tumor cells. Our results suggest that RANKL expression may have a role in the pathogenesis of GCTBs and in the formation of the large OC population present in these tumors.
Roux
Sophie
S
Rheumatology Department, Bicêtre Hospital, Le Kremlin-Bicêtre, France.
Amazit
Larbi
L
Meduri
Geri
G
Guiochon-Mantel
Anne
A
Milgrom
Edwin
E
Mariette
Xavier
X
D000818:Animals; D000918:Antibody Specificity; D019556:COS Cells; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D002452:Cell Count; D018076:DNA, Complementary / Q000378:metabolism; D015870:Gene Expression; D018212:Giant Cell Tumor of Bone / Q000378:metabolism* / Q000473:pathology*; D006023:Glycoproteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor; D014162:Transfection
D002352:Carrier Proteins; D018076:DNA, Complementary; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D017493:Leukocyte Common Antigens