Matrix metalloproteinase 9 (gelatinase B) is expressed in multinucleated giant cells of human giant cell tumor of bone and is associated with vascular invasion

Yoshimichi Ueda, Kazushi Imai, Hiroyuki Tsuchiya, Noboru Fujimoto, Isao Nakanishi, Shogo Katsuda, Motoharu Seiki, Yasunori Okada

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Abstract

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.

Original languageEnglish
Pages (from-to)611-622
Number of pages12
JournalAmerican Journal of Pathology
Volume148
Issue number2
Publication statusPublished - 1996 Feb
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Ueda, Y., Imai, K., Tsuchiya, H., Fujimoto, N., Nakanishi, I., Katsuda, S., Seiki, M., & Okada, Y. (1996). Matrix metalloproteinase 9 (gelatinase B) is expressed in multinucleated giant cells of human giant cell tumor of bone and is associated with vascular invasion. American Journal of Pathology, 148(2), 611-622.