Collagenase expression and activity in the stromal cells from giant cell tumour of bone

• Published in: Bone (New York, N.Y.) Vol. 44; no. 5; pp. 865 - 871
• Main Authors: Cowan, Robert W, Mak, Isabella W.Y, Colterjohn, Nigel, Singh, Gurmit, Ghert, Michelle
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.05.2009; Elsevier
• Subjects: Adult; Biological and medical sciences; Blotting, Western; Collagen; Collagenases - genetics; Collagenases - metabolism; Female; Fundamental and applied biological sciences. Psychology; Giant Cell Tumor of Bone - genetics; Giant Cell Tumor of Bone - metabolism; Giant cell tumour; Humans; Immunohistochemistry; Male; Matrix Metalloproteinase 1 - genetics; Matrix Metalloproteinase 1 - metabolism; Matrix Metalloproteinase 13 - genetics; Matrix Metalloproteinase 13 - metabolism; Matrix Metalloproteinase 8 - genetics; Matrix Metalloproteinase 8 - metabolism; Matrix metalloproteinases; Middle Aged; Orthopedics; Osteolysis; Reverse Transcriptase Polymerase Chain Reaction; Stromal cells; Stromal Cells - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Giant cell tumour; Matrix metalloproteinases; Osteolysis; Stromal cells; Collagen; Giant cell tumor; Morphology; Stromal cell; Bone
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2009.01.393

Abstract The characteristic bone destruction in giant cell tumour of bone (GCT) is largely attributed to the osteoclast-like giant cells. However, experimental analyses of bone resorption by cells from GCT often fail to exclude the neoplastic spindle-like stromal cells, and several studies have demonstrated that bone resorption by GCT cells is increased in the presence of stromal cells. The spindle-like stromal cells from GCT may therefore actively contribute to the bone resorption observed in the tumour. Type I collagen, a major organic constituent of bone, is effectively degraded by three matrix metalloproteinases (MMPs) known as the collagenases: MMP-1, MMP-8 and MMP-13. We established primary cell cultures from nine patients with GCT and the stromal cell populations were isolated in culture. The production of collagenases by primary cultures of GCT stromal cells was determined through real-time PCR, western blot analysis and a multiplex assay system. Results show that the cells produce MMP-1 and MMP-13 but not MMP-8. Immunohistochemistry confirmed the presence of MMP-1 and MMP-13 in paraffin-embedded GCT tissue samples. Medium conditioned by the stromal cell cultures was capable of proteolytic activity as determined by MMP-1 and MMP-13-specific standardized enzyme activity assays. The spindle-like stromal cells from GCT may therefore actively participate in the bone destruction that is characteristic of the tumour.