title: Enhanced production of osteopontin in multiple myeloma: clinical and pathogenic implications.
abstract: In this study, we examined osteopontin (OPN) production in myeloma cells and plasma OPN levels in multiple myeloma (MM) patients. We assessed OPN production in bone marrow cells (BMCs) by immunocytochemistry and enzyme-linked immunosorbent assay (ELISA). We also assessed OPN production in various B-cell malignant cell lines, including three myeloma cell lines by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. In addition, we measured plasma OPN concentrations by ELISA in 30 MM patients, 21 monoclonal gammopathy of undetermined significance (MGUS) patients and 30 healthy volunteers. As a result, in an immunocytochemical study, abundant OPN was detected in BMCs from overt MM patients, whereas no OPN was detected in BMCs from patients with other haematological diseases, including MGUS. Cultured BMCs from overt MM patients produced more OPN than those from patients with either smouldering MM or MGUS. Myeloma cell lines spontaneously produced OPN. Plasma OPN levels of MM patients were significantly higher than those of MGUS patients and healthy volunteers (P < 0.05). Moreover, they correlated with both progression and bone destruction of the disease (P < 0.05). These suggest that myeloma cells actively produce OPN, which possibly contributes to osteoclastic bone resorption in MM. Plasma OPN levels may be a useful biomarker for assessing bone destruction in MM and distinguishing MM from MGUS or smouldering MM.
authors.affiliation: Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. saekiy@omh.hosp.go.jp
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Saeki
authors.forename: Toru
authors.initials: T
authors.lastname: Mima
authors.forename: Taeko
authors.initials: T
authors.lastname: Ishii
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ogata
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Shiro
authors.initials: S
authors.lastname: Ohshima
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Ishida
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Tabunoki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kitayama
authors.forename: Masao
authors.initials: M
authors.lastname: Mizuki
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Katada
authors.forename: Hideki
authors.initials: H
authors.lastname: Asaoku
authors.forename: Masayasu
authors.initials: M
authors.lastname: Kitano
authors.forename: Norihiro
authors.initials: N
authors.lastname: Nishimoto
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Yoshizaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Maeda
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kon
authors.forename: Naokazu
authors.initials: N
authors.lastname: Kinoshita
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Uede
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawase
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000097:blood; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism; D001862:Bone Resorption / Q000097:blood / Q000209:etiology; D003937:Diagnosis, Differential; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009101:Multiple Myeloma / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000097:blood / Q000502:physiology; D009367:Neoplasm Staging; D053495:Osteopontin; D010265:Paraproteinemias / Q000097:blood / Q000175:diagnosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000097:blood / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin