title: TRAIL produced from multiple myeloma cells is associated with osteolytic             markers.
abstract: Skeletal complications represent major clinical problems in multiple myeloma             (MM). MM cells are known to induce differentiation of osteoclasts and inhibit             osteoblasts. Receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin             (OPG) are key molecules for osteoclastogenesis. Although OPG interacts with tumor             necrosis factor-related apoptosis-inducing ligand (TRAIL), the contribution of             TRAIL to skeletal-related events (SRE) remains a matter of debate. In the present             study, we examined the role of TRAIL in MM bone lesions. Myeloma cells were purified             from 56 MM patients by CD138-immunomagnetic beads. TRAIL, DKK-1 and MIP1α RNA             expression in purified MM cells was analyzed by real-time PCR. Immunohistochemistry             of TRAIL was performed on paraffin-embedded plasmacytoma tissue sections. The             concentration of TRAIL in the serum and bone marrow plasma from MM patients was             analyzed by ELISA. TRAIL expression was significantly higher in MM cells than             in plasma cells from patients with monoclonal gammopathy of undetermined significance             (MGUS). TRAIL staining was detected in the cytoplasm of myeloma cells. TRAIL expression             in MM cells correlated with bone marrow plasma TRAIL concentration. TRAIL expression             had a positive correlation with osteolytic markers, such as serum calcium and             urinary deoxypyridinoline. These results suggest that TRAIL, produced from myeloma             cells, may play an important role in bone resorption of MM patients. Inhibition             of this pathway may lead to development of a new therapeutic approach preventing             bone resorption in MM.
authors: Department of Hematology, Kumamoto University School of Medicine, and Department of Surgical Pathology, Kumamoto University Hospital, Kumamoto, Japan.
authors: Yawara
authors: Y
authors: Kawano
authors: Shikiko
authors: S
authors: Ueno
authors: Masahiro
authors: M
authors: Abe
authors: Yoshitaka
authors: Y
authors: Kikukawa
authors: Hiromichi
authors: H
authors: Yuki
authors: Kenichi
authors: K
authors: Iyama
authors: Yutaka
authors: Y
authors: Okuno
authors: Hiroaki
authors: H
authors: Mitsuya
authors: Hiroyuki
authors: H
authors: Hata
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000652:urine; D002118:Calcium / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology*; D010014:Osteolysis / Q000378:metabolism* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C036020:deoxypyridinoline; D002118:Calcium