Osteoclast-like cell formation by circulating myeloma B lymphocytes: role of RANK-L.
Excessive bone resorption in multiple myeloma (MM), a malignancy of B lymphoid origin, is mediated through osteoclasts, which respond to local osteoclast-activating factors produced by tumor cells within the bone marrow microenvironment. Direct bone resorption by myeloma cells is investigated in the present study, since a connection between B lymphocytes and osteoclast differentiation pathways has been recently postulated in mice. Peripheral CD19+ B lymphocytes isolated from 10 myeloma patients with multiple osteolytic lesions and 10 healthy donors were cultured in the presence of M-CSF and RANK-L, two major osteoclast-activating factors. The TRAP expression and resorption of bone substrates were employed to evaluate osteoclast differentiation. MM patients were characterized by the presence of circulating B lymphocytes endowed with both phenotypical and functional properties of osteoclast-like cells in vitro when stimulated with RANK-L. The absence of these characteristics in B lymphocytes from healthy donors indicates that the transformation can be ascribed to the presence of clonogenic B cells in patients with MM. Clonotypic B lymphocytes may contribute to the pathogenesis of bone disease in MM by acting as RANK-L-dependent osteoclast progenitors.
Calvani
Nicola
N
DIMO, Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari, Piazza G. Cesare, 11-70124 Bari, Italy.
Silvestris
Franco
F
Cafforio
Paola
P
Dammacco
Franco
F
D000368:Aged; D018941:Antigens, CD19 / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000378:metabolism*; D001862:Bone Resorption; D002352:Carrier Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D002455:Cell Division; D002478:Cells, Cultured; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism*; D009360:Neoplastic Cells, Circulating; D010010:Osteoclasts / Q000378:metabolism*; D010641:Phenotype; D053245:RANK Ligand; D012333:RNA, Messenger / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018941:Antigens, CD19; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D016173:Macrophage Colony-Stimulating Factor