Matrix metalloproteinase 9 (gelatinase B) is expressed in multinucleated giant cells of human giant cell tumor of bone and is associated with vascular invasion.
Human giant cell tumor (GCT) consists of multinucleated giant cells and mononuclear stromal cells, and is characterized by frequent vascular invasion without distant metastases. To study the role of matrix metalloproteinases (MMPs) in the vascular invasion, we examined production of MMP-1 (tissue collagenase), -2 (gelatinase A), -3 (stromelysin-1), -9 (gelatinase B), and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in GCT. MMP-9 was highly and predominantly expressed in giant cells by both immunohistochemistry and in situ hybridization. Expression of other MMPs was also observed in some cases but was inconstant. Sandwich enzyme immunoassays demonstrated that MMP-9 is the predominant MMP secreted by GCT. There was a definite imbalance between the amounts of MMP-9 and those of TIMPs in the culture media of GCT, leading to detectable gelatinolytic activity in an assay using 14C-gelatin. Gelatin zymography demonstrated the main activity at about 90 kd, which was identified as the zymogen of MMP-9 by immunoblotting. Immunohistochemistry for type IV collagen and laminin, major basement membrane components, showed that disappearance of the proteins is closely associated with MMP-9-positive giant cells. These results indicate the production of MMP-9 by multinucleated giant cells and suggest that the metalloproteinase may contribute to proteolysis associated with vascular invasion and local bone resorption in human GCT.
Ueda
Y
Y
Department of Pathology, Kanazawa Medical University, Uchinada, Japan.
Imai
K
K
Tsuchiya
H
H
Fujimoto
N
N
Nakanishi
I
I
Katsuda
S
S
Seiki
M
M
Okada
Y
Y
D000293:Adolescent; D000328:Adult; D001485:Basement Membrane / Q000737:chemistry / Q000473:pathology; D001859:Bone Neoplasms / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D017364:Collagenases / Q000032:analysis / Q000096:biosynthesis*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005500:Follow-Up Studies; D018212:Giant Cell Tumor of Bone / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D015726:Giant Cells / Q000201:enzymology*; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008297:Male; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000032:analysis; D008875:Middle Aged; D008985:Monensin / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D011480:Protease Inhibitors / Q000032:analysis; D011506:Proteins / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D011480:Protease Inhibitors; D011506:Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D008985:Monensin; D017364:Collagenases; D008666:Metalloendopeptidases; D020780:Matrix Metalloproteinase 9