CANINE OSTEOSARCOMA CELLS EXPRESS MMP-9 THROUGH CELL-MATRIX

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To investigate the participation of MMP-9 in the formation of lung metastasis, we have established an animal model for lung metastasis by the injection of osteosarcoma (OS) cells into mammary fad pad of SCID mice. Gelatinzymography revealed a great deal of MMP-9 secreted by the lung tissues containing metastatic lesions, whereas only MMP-2 was detected in 'hypothetic' origin these results suggested that OS cells could acquire the ability of MMP-9 expression during tumor invasion and metastasis. Therefore, we examined the mechanism of MMP-9 expression under several culture condition in vitro. In monolayer culture of OS cells on several extracellular matrix, MMP-9 was not detected by gelatin zymography, while MMP-2 was constantly expressed. When OS cells were cultivated in type I collagen gel, MMP-9 was apparently detected in addition of MMP-2. The expression of MMP-9 in collagen gel was down-regulated by anti-integrin antibodies and cytochalasin D. Thus, we suggested that the expression of MMP-9 by OS cells was regulated through integrin-mediated cell-matrix interaction and following actin polymerization.