CANINE OSTEOSARCOMA CELLS EXPRESS MMP-9 THROUGH CELL-MATRIX

为了探讨MMP-9在肺转移形成中的作用，我们通过将骨肉瘤细胞注射到SCID小鼠乳腺衬垫，建立了肺转移动物模型。明胶酶谱图显示含有转移灶的肺组织分泌大量MMP-9，而在“假设”起源中仅检测到MMP-2，这些结果表明OS细胞在肿瘤侵袭和转移过程中可以获得MMP-9的表达能力。因此，我们在几种体外培养条件下考察了MMP-9的表达机制。在多种细胞外基质上单层培养的OS细胞中，明胶酶谱法未检测到MMP-9，而MMP-2持续表达。当OS细胞在I型胶原凝胶中培养时，除了MMP-2外，还明显检测到MMP-9。抗整合素抗体和细胞松弛素d可下调胶原凝胶中MMP-9的表达，因此，我们认为OS细胞中MMP-9的表达是通过整合素介导的细胞-基质相互作用和肌动蛋白聚合来调节的。

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.