2007 WINNER OF THE ALEXANDRA KIRKLEY AWARD
SECOND PRIZE

Protease Activity in the Stromal Cells of Giant Cell Tumour of Bone

Alexander Rabinovich, M.D.
London, ON

R. Cowan
N. Simunovic
N. Colterjohn
G. Singh
M. Ghert

Giant cell tumour (GCT) of bone is an osteolytic tumour that is locally aggressive and potentially metastatic. Although the osteoclast-like giant cells have classically been considered the main culprits in bone destruction, the stromal cells are believed to be the neoplastic element of the tumour. Matrix metalloproteinases (MMP-2, MMP-9) are proteases involved in degradation and remodeling of bone matrix, and have been implicated in tumour aggressiveness. In this study, we successfully harvested and cultivated primary cell lines from clinical specimens of GCT of bone. We characterized the cells to be of mesenchymal origin and to produce activated MMP-2 and MMP-9 in vitro. We therefore conclude that the stromal cells of GCT of bone may play a key role in bone destruction through a matrix metalloproteinase mechanism. These results are intriguing, as novel therapies in specific MMP inhibitors are currently underway for numerous disease processes.