Enhanced production of osteopontin in multiple myeloma: clinical and pathogenic implications.
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.
Saeki
Yukihiko
Y
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. saekiy@omh.hosp.go.jp
Mima
Toru
T
Ishii
Taeko
T
Ogata
Atsushi
A
Kobayashi
Hideyuki
H
Ohshima
Shiro
S
Ishida
Tetsushi
T
Tabunoki
Yuichiro
Y
Kitayama
Hitoshi
H
Mizuki
Masao
M
Katada
Yoshinori
Y
Asaoku
Hideki
H
Kitano
Masayasu
M
Nishimoto
Norihiro
N
Yoshizaki
Kazuyuki
K
Maeda
Masahiro
M
Kon
Shigeyuki
S
Kinoshita
Naokazu
N
Uede
Toshimitsu
T
Kawase
Ichiro
I
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
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin