Ability of myeloma cells to secrete macrophage inflammatory protein (MIP)-1alpha and MIP-1beta correlates with lytic bone lesions in patients with multiple myeloma.
Macrophage inflammatory protein (MIP)-1alpha and MIP-1beta have been identified as candidates for multiple myeloma (MM)-derived bone-resorbing factors. To validate the clinical relevance of these observations, we investigated correlations between the ability of MM cells to secrete these chemokines and the extent of MM bone lesions as well as levels of biochemical bone markers in patients with MM. Patients with multiple bone lesions exhibited higher MIP-1alpha and MIP-1beta secretion from MM cells along with elevated urinary deoxypyridinoline (Dpd), without significant elevation of serum bone-specific alkaline phosphatase (BALP) or osteocalcin compared with those with minimal bone lesions. MIP-1alpha and MIP-1beta levels correlated positively with urinary Dpd and serum BALP but not with serum osteocalcin. These results provide further evidence for a causal role of MIP-1alpha and MIP-1beta in the development of lytic bone lesions, and suggest that MM cells suppress osteoblastic bone formation to cause an imbalance of bone turnover and development of destructive bone lesions.
Hashimoto
Toshihiro
T
Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine Division of Transfusion Medicine, Tokushima University Hospital, Tokushima, Japan.
Abe
Masahiro
M
Oshima
Takashi
T
Shibata
Hironobu
H
Ozaki
Shuji
S
Inoue
Daisuke
D
Matsumoto
Toshio
T
D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D015415:Biomarkers / Q000032:analysis; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D005260:Female; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000378:metabolism*; D015675:Osteocalcin / Q000097:blood; D010014:Osteolysis / Q000209:etiology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D015415:Biomarkers; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D015675:Osteocalcin; C036020:deoxypyridinoline; D000469:Alkaline Phosphatase