Connective tissue growth factor is an indicator of bone involvement in multiple myeloma, but matrix metalloproteinase-9 is not.
Bone disease (BD) in multiple myeloma (MM) is because of the activation of osteoclasts and impairment of osteoblast differentiation. Connective tissue growth factor (CTGF) is known to participate in the differentiation of mesenchymal stem cells to committed osteoprogenitor cells. We analysed the concentration of circulating CTGF in 35 MM patients and 22 malignant lymphoma (ML) patients and 14 normal individuals. CTGF is protease-sensitive and thus is found as both an N-terminal half fragment (N-half CTGF) and whole (W-CTGF). Serum levels of W-CTGF and N-half CTGF + W-CTGF were determined by separate sandwich enzyme-linked immunosorbent assays. The level of W-CTGF was significantly lower (P < 0.005) in MM patients compared with ML patients and normal individuals, while N-half + W-CTGF was similar in all groups. Furthermore, W-CTGF was significantly lower in MM patients with BD compared with those without BD (P < 0.005) and this was independent of previous treatment. Matrix metalloproteinase (MMP)-9 is produced by myeloma cells and is thought to be related to BD in MM. However, MMP-9 does not cleave CTGF and serum MMP-9 level was not related to BD in MM. Thus, CTGF is an indicator of BD in MM; its metabolism and function in MM should be clarified.
Munemasa
Shoso
S
Department of Haematology and Oncology, RIRBM, Hiroshima University, Hiroshima, Japan.
Sakai
Akira
A
Kuroda
Yoshiaki
Y
Okikawa
Yoshiko
Y
Katayama
Yuta
Y
Asaoku
Hideki
H
Kubo
Tadahiko
T
Miyakawa
Yoshitaka
Y
Serikawa
Masahiro
M
Sasaki
Tamito
T
Kimura
Akiro
A
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001853:Bone Marrow / Q000737:chemistry / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D055513:Connective Tissue Growth Factor; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000097:blood* / Q000235:genetics / Q000494:pharmacology; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics / Q000494:pharmacology; D008223:Lymphoma / Q000097:blood; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D055513:Connective Tissue Growth Factor; D053509:Matrix Metalloproteinase 13; D020780:Matrix Metalloproteinase 9