Regulation of MMP-2 and MMP-9 Expression in Childhood Osteosarcoma by Inducers and Inhibitors #95

M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Dr. Rath Research Institute, Cancer Division, Santa Clara, CA 95050, USA

Presented at: 
International Society for Biological Therapy of Cancer, Nov 10-13, 2005, Alexandria, VA

Published in: 
International Society for Biological Therapy of Cancer Proceedings, Abstract #95



Osteosarcoma, the most frequent malignant bone tumor of childhood, is highly invasive, leading to pulmonary metastases and eventual death, despite conventional chemotherapy and surgical treatments. Degradation of the extracellular matrix, which leads to invasion and metastasis occurs secondary to secretion of matrix metalloproteinases (MMPs), in particular MMP-2 and MMP-9. In this study the inducers and inhibitors of MMP-2 and –9 by osteosarcoma U-20S cells were studied in vitro. MMP-2 secretion by osteosarcoma cell line U-2OS was not influenced by PMA, cytokines and LPS. However, the induction of MMP-9 was associated with the inducer used, strongest with PMA, followed by cytokines, and least with LPS. MMP-2 and MMP-9 were down regulated with inhibitors. These results are important since they indicate that inhibitors such as EGCG, doxycycline and others have a significant inhibitory effect on osteosarcoma MMP-2 and MMP-9 secretion in vitro, and thus have potential in treatment of osteosarcoma.