These findings demonstrate that zaltoprofen could be a promising drug against the malignant phenotypes in chondrosarcomas via activation of PPARγ and inhibition of MMP2 activity.
As demonstrated by the transwell, immunoblotting, and real-time PCR analyses, we found that S1P inhibited cell migration and MMP-2 expression through the upregulation of the tissue inhibitor of metalloproteinase-3 (TIMP-3) expression in human chondrosarcoma cells.
We also found that HGF increased the migration and expression of matrix metalloproteinase (MMP)-2 in human chondrosarcoma cells. c-Met inhibitor and siRNA reduced HGF-increased cell migration and MMP-2 expression.
This data suggests that ETV5 has a significant role in regulating MMP2 expression and therefore matrix resorption in human chondrosarcoma, and thus may be a targetable upstream effector of the metastatic cascade in this cancer.
Our findings suggest that alendronate may reduce MMP-2 secretion at the transcriptional and translational levels, and inhibit the invasion of chondrosarcoma cell.